Apoptosis is vital for improving the efficacy of lung cancer (LC) immunotherapy by targeting cancer cell elimination. Despite its importance, there is a lack of comprehensive bibliometric studies analyzing global research on apoptosis in LC immunotherapy. This analysis aims to address this gap by highlighting key trends, contributors, and future directions. A total of 969 publications from 1996 to 2024 were extracted from the Web of Science Core Collection. Analysis was conducted using VOSviewer, CiteSpace, and the R package 'bibliometrix.' The study included contributions from 6,894 researchers across 1,469 institutions in 61 countries, with research published in 356 journals. The volume of publications has steadily increased, led by China and the United States, with Sichuan University as the top contributor. The journal Cancers published the most articles, while Cancer Research had the highest co-citations. Yu-Quan Wei was the leading author, and Jemal, A. was the most frequently co-cited. Key research themes include "cell death mechanisms," "immune regulation," "combination therapies," "gene and nanomedicine applications," and "traditional Chinese medicine (TCM)." Future research is likely to focus on "coordinated regulation of multiple cell death pathways," "modulation of the tumor immune microenvironment," "optimization of combination therapies," "novel strategies in gene regulation," and the "integration of TCM" for personalized treatment. This is the first bibliometric analysis on the role of apoptosis in LC immunotherapy, providing an landscape of global research patterns and emerging therapeutic strategies. The findings offer insights to guide future research and optimize treatment approaches.

The present study aimed to investigate how sevoflurane (SEV) regulated the apoptosis of glioma cells through the mitochondrial apoptosis pathway. First, an evaluation was performed on the viability, apoptosis, mitochondrial reactive oxygen species levels, mitochondrial membrane potential and apoptosis and autophagy‑related protein expression of glioma cells according to experimental groups. Next, the expression of microRNA‑211‑5p (miR‑211‑5p), silent information regulator 1 (SIRT1) and phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway was detected by reverse transcription‑quantitative PCR or western blotting. Dual luciferase reporter gene assay confirmed the targeting relationship between miR‑211‑5p and SIRT1. In addition, SEV suppressed the proliferation and induced the apoptosis in human glioma cell line cells via the mitochondrial apoptosis pathway. In mechanistic analysis, the miR‑211‑5p level in glioma cells was low, while following SEV treatment, it was increased. Furthermore, SEV regulated SIRT1 by upregulating miR‑211‑5p expression, thereby blocking the PI3K/AKT signaling pathway activation. Moreover, functional rescue experiments showed that downregulation of SIRT1 or miR‑211‑5p could reverse the effects of SEV on glioma cells. Collectively, SEV promoted apoptosis in glioma cells by inducing miR‑211‑5p, which regulated SIRT1/PI3K/AKT pathway, mediating mitochondria‑dependent apoptosis pathway. This finding may open new possibilities for SEV as a potential treatment for glioma in the future.

Salvia miltiorrhiza Bunge (Salvia miltiorrhiza), commonly referred to as Danshen, is a well‑known herb in traditional Chinese medicine, the active ingredients of which are mostly categorized as water soluble and lipid soluble. Salvianolic acids are the major water‑soluble phenolic acid constituents of Danshen; salvianolic acid B is the most prevalent, with salvianolic acid A (SAA) being the next most predominant form. SAA offers a wide array of pharmacological benefits, including cardiovascular protection, and anti‑inflammatory, antioxidant, antiviral and anticancer activities. SAA is currently undergoing phase III clinical trials for diabetic peripheral neuropathy and has shown protective benefits against cardiovascular illnesses; furthermore, its safety and effectiveness are encouraging. By targeting several signaling pathways, preventing cell cycle progression, tumor cell migration, invasion and metastasis, normalizing the tumor vasculature and encouraging cell apoptosis, SAA can also prevent the growth of malignancies. In addition, it enhances sensitivity to chemotherapeutic drugs, and alleviates their toxicity and side effects. However, the broad therapeutic use of SAA has been somewhat limited by its low content in Salvia miltiorrhiza Bunge and the difficulty of its extraction techniques. Therefore, the present review focuses on the potential mechanisms of SAA in tumor prevention and treatment. With the anticipation that SAA will serve a notable role in clinical applications in the future, these discoveries may offer a scientific basis for the combination of SAA with conventional chemotherapeutic drugs in the treatment of cancer, and could establish a foundation for the development of SAA as an anticancer drug.

Osteosarcoma (OS), frequently observed in children and adolescents, is one of the most common primary malignant tumors of the bone known to be associated with a high capacity for invasion and metastasis. The incidence of osteosarcoma in children and adolescents is growing annually, although improvements in survival remain limited. With the clinical application of neoadjuvant chemotherapy, chemotherapy combined with limb-preserving surgery has gained momentum as a major intervention. However, certain patients with OS experience treatment failure owing to chemoradiotherapy resistance or metastasis. Nuclear factor E2-related factor 2 (Nrf2), a key antioxidant factor in organisms, plays a crucial role in maintaining cellular physiological homeostasis; however, its overactivation in cancer cells restricts reactive oxygen species production, promotes DNA repair and drug efflux, and ultimately leads to chemoradiotherapy resistance. Recent studies have also identified the functions of Nrf2 beyond its antioxidative function, including the promotion of proliferation, metastasis, and regulation of metabolism. The current review describes the multiple mechanisms of chemoradiotherapy resistance in OS and the substantial role of Nrf2 in the signaling regulatory network to elucidate the function of Nrf2 in promoting OS chemoradiotherapy resistance and formulating relevant therapeutic strategies.

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression. Among these, miR-660, located on chromosome Xp11.23, is increasingly studied for its role in cancer due to its abnormal expression in various biological contexts. It is regulated by 8 competing endogenous RNAs (ceRNAs), which adds complexity to its function. miR- 660 targets 19 genes involved in 6 pathways such as PI3K/AKT/mTOR, STAT3, Wnt/β-catenin, p53, NF‑κB, and RAS, influencing cell cycle, proliferation, apoptosis, and invasion/migration. It also plays a role in resistance to chemotherapies like cisplatin, gemcitabine, and sorafenib in lung adenocarcinoma (LUAD), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC), thus highlighting its clinical importance. Additionally, leveraging liposomes as nanocarriers presents a promising avenue for enhancing cancer drug delivery. Our comprehensive study not only elucidates the aberrant expression patterns, biological functions, and regulatory networks of miR-660 and its ceRNAs but also delves into the intricate signaling pathways implicated. We envisage that our findings will furnish a robust framework and serve as a seminal reference for future investigations of miR-660, fostering advancements in cancer research and potentially catalyzing breakthroughs in cancer diagnosis and treatment paradigms.

Rhein is one of the main bioactive compounds in the Polygonaceae plant, and has been proven to have anti-cancer activity in some reports. But the mechanism of Rhein in the treatment of gastric cancer (GC) is limited reported. In this research, network pharmacology combined with in vitro experiments was used for systematically studying the mechanism of Rhein.

Network pharmacology confirmed the major effect signaling pathway and key targets of Rhein in the treatment of GC. Cell viability assay, colony formation assay, fluorescence probe assay, apoptosis assay, western blot and qRT-PCR verified the mechanism of Rhein in the treatment of GC cells (AGS and MGC803 cells).

The results showed that Rhein significantly induced the apoptosis process of AGS and MGC803 cells by regulating the Ras/phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and the p38/mitogen-activated protein kinase signaling pathways. The AKT activator (SC79) and p38 inhibitor (SB202190) inhibited Rhein-induced apoptosis.

All results proved that Rhein could be recognized as a potential natural drug for the treatment of GC.

PD15, a novel natural steroidal saponin extracted from the rhizomes of Paris delavayi Franchet, has demonstrated a strong cytotoxic effect against HepG2 and U87MG cells. However, its therapeutic effects on colorectal cancer (CRC) and the underlying molecular mechanisms remain unclear.

MTT assay, clonogenic assay, Hoechst 33258 staining, flow cytometry, molecular docking, and western blot were used to investigate the mechanism of PD15 in HCT116 cell lines. Additionally, the anti-CRC effects of PD15 were evaluated in vivo using HCT116 xenograft models.

PD15 significantly inhibited cell proliferation and induced G0/G1 phase arrest in HCT116 cells. Furthermore, PD15 upregulated cleaved Caspase 3 and 9, cleaved PARP, and Bax expression levels while downregulating Bcl-2, leading to apoptosis. Further experiments revealed that PD15 downregulated the protein expression of p-Akt and p-GSK3β, with LY294002 (a PI3K/Akt inhibitor) enhancing PD15-induced apoptosis and its effects on Akt/GSK3β-associated proteins. In addition, molecular docking demonstrated that PD15 exhibited strong binding affinity with Akt and GSK3β. Critically, PD15 inhibited CRC growth in vivo without causing apparent toxicity in mice.

These findings indicate that PD15 could trigger apoptosis by suppressing the Akt/GSK3β signaling pathway in HCT116 cells.

Breast cancer (BC) and gynecological malignancies, including cervical, ovarian, and uterine cancers, are significant global health challenges due to their high prevalence, complex nature, and elevated mortality rates. Dysregulation of the Wnt/β-catenin signaling pathway is a common feature in gynecological malignancies, contributing to cancer cell growth, progression, migration, and metastasis. Recent studies have highlighted the pivotal role of non-coding RNAs (ncRNAs), particularly circular RNAs (circRNAs), in modulating the Wnt/β-catenin signaling pathway. Acting as sponges for microRNAs (miRNAs), circRNAs regulate key oncogenic and tumor-suppressive processes by influencing Wnt-related components. This research explores the role of circRNAs in breast and gynecological malignancies, focusing on their regulatory effects on the Wnt/β-catenin pathway. The findings reveal that circRNAs modulate critical cellular processes such as proliferation, apoptosis, autophagy, and metastasis, with potential implications for therapeutic interventions. Targeting circRNA-mediated dysregulation of Wnt signaling could offer novel strategies for improving diagnostic precision, treatment efficacy, and survival outcomes in breast and gynecological cancers.

Castration-resistant prostate cancer (CRPC) presents a significant challenge due to its resistance to conventional androgen deprivation therapies. Urolithins, bioactive metabolites derived from ellagitannins, have recently emerged as promising therapeutic agents for CRPC. Urolithins not only inhibit androgen receptor (AR) signaling, a crucial factor in the progression of CRPC, but also play a key role in regulating oxidative stress by their antioxidant properties, thereby inhibiting increased reactive oxygen species, a common feature of the aggressive nature of CRPC. Research has shown that urolithins induce apoptosis and diminish pro-survival signaling, leading to tumor inhibition. This review delves into the intricate mechanisms through which urolithins exert their therapeutic effects, focusing on both AR-dependent and AR-independent pathways. It also explores the exciting potential of combining urolithins with androgen ablation therapy, opening new avenues for CRPC treatment.

Globally, colorectal cancer (CRC) is the third most common type of cancer, and its treatment frequently includes the utilization of drugs based on antibodies and small molecules. The development of CRC has been linked to various signaling pathways, with the Wnt/β-catenin pathway identified as a key target for intervention.

We have explored the impact of imidazopyridine-tethered chalcone-C (CHL-C) in CRC models.

To determine the influence of CHL-C on apoptosis and autophagy, Western blot analysis, annexin V assay, cell cycle analysis, acridine orange staining, and immunocytochemistry were performed. Next, the activation of the Wnt/β-catenin signaling pathway and the anti-cancer effects of CHL-C in vivo were examined in an orthotopic HCT-116 mouse model.

We describe the synthesis and biological assessment of the CHL series as inhibitors of the viability of HCT-116, SW480, HT-29, HCT-15, and SNU-C2A CRC cell lines. Further biological evaluations showed that CHL-C induced apoptosis and autophagy in down-regulated β-catenin, Wnt3a, FZD-1, Axin-1, and p-GSK-3β (Ser9), and up-regulated p-GSK3β (Tyr216) and β-TrCP. In-depth analysis using structure-based bioinformatics showed that CHL-C strongly binds to β-catenin, with a binding affinity comparable to that of ICG-001, a well-known β-catenin inhibitor. Additionally, our in vivo research showed that CHL-C markedly inhibited tumor growth and triggered the activation of both apoptosis and autophagy in tumor tissues.

CHL-C is capable of inducing apoptosis and autophagy by influencing the Wnt/β-catenin signaling pathway.

The objective of this study was to isolate and characterize a cytotoxic compound from the hydromethanolic extract of Dalbergia sissoo Roxb. ex DC. leaves using the cold percolation technique. Thin-layer chromatography was employed to isolate the cytotoxic component from the crude plant extract, and its cytotoxicity against lung adenocarcinoma (A549) cells was evaluated using the MTT assay. The structure of the isolated cytotoxic compound was determined through FTIR, NMR, UV analysis, and LC-MS/MS methods. Through comprehensive characterization, a cytotoxic compound called Biochanin A (BA) was identified, exhibiting significant anticancer activity with an IC50 value of 21.92 ± 2.19 μM against A549 cells, while demonstrating lower cytotoxicity towards normal lung cells (WI-38) with an IC50 value of 285.12 ± 2.19 μM. Notably, BA induced morphological changes in A549 cells, leading to apoptotic alterations and the generation of reactive oxygen species (ROS), as confirmed by multiple techniques (AO/EB, DAPI, Giemsa). In silico molecular docking, ADMET, MMGBSA, and molecular dynamics simulation investigations support the RT-PCR and cell biology findings. As a result, BA's molecular mechanism of action involves ROS-induced apoptosis mediated by caspases 9 and 3.

Cancer stem cells (CSCs) constitute a small yet crucial subgroup in tumors, known for their capacity to self-renew, differentiate, and promote tumor growth, metastasis, and resistance to therapy. These characteristics position CSCs as significant factors in tumor recurrence and unfavorable clinical results, emphasizing their role as targets for therapy. Autophagy, an evolutionarily preserved cellular mechanism for degradation and recycling, has a complex function in cancer by aiding cell survival during stress and preserving balance by eliminating damaged organelles and proteins. Although autophagy can hinder tumor growth by reducing genomic instability, it also aids tumor advancement, particularly in harsh microenvironments, highlighting its dual characteristics. Recent research has highlighted the complex interactions between autophagy and CSCs, showing that autophagy governs CSC maintenance, boosts survival, and aids in resistance to chemotherapy and radiotherapy. On the other hand, in specific situations, autophagy may restrict CSC growth by increasing differentiation or inducing cell death. These intricate interactions offer both obstacles and possibilities for therapeutic intervention. Pharmacological modulation of autophagy, via inhibitors like chloroquine or by enhancing autophagy when advantageous, has demonstrated potential in making CSCs more responsive to standard treatments. Nonetheless, applying these strategies in clinical settings necessitates a better understanding of context-dependent autophagy dynamics and the discovery of dependable biomarkers indicating autophagic activity in CSCs. Progressing in this area might unveil novel, accurate strategies to tackle therapy resistance, lessen tumor recurrence, and ultimately enhance patient outcomes.

Colorectal cancer (CRC) remains a malignancy with high incidence and mortality rates worldwide, necessitating the development of more effective therapeutic strategies due to the limitations of current treatments, including drug resistance and adverse effects. Scutellaria baicalensis, a traditional Chinese medicinal herb, contains baicalin and baicalein as its primary bioactive flavonoids, which exhibit notable pharmacological properties such as antibacterial, anti-inflammatory, antioxidant, and antitumor effects. Recent studies have demonstrated that baicalin and baicalein show promising antitumor activity in CRC treatment through mechanisms such as scavenging reactive oxygen species, immune regulation, and inhibition of tumor cell proliferation, induction of apoptosis, and modulation of the gut microenvironment. This study further investigates the molecular mechanisms underlying the therapeutic effects of baicalin and baicalein in CRC, aiming to provide new research perspectives and potential clinical applications for the integration of flavonoid-based compounds from Scutellaria baicalensis in CRC treatment.

Lung cancer continues to be a primary contributor to cancer-related deaths globally, and multidrug resistance (MDR) poses a significant obstacle in its management. Traditional Chinese medicines (TCMs), recognized for their comprehensive therapeutic strategies and low incidence of adverse effects, have garnered attention due to their capacity to mitigate MDR in cancer cells. Nevertheless, deciphering the precise mechanisms through which TCMs reverse MDR in lung cancer presents a substantial scientific challenge. The objective of this review is to examine prevalent manifestations of MDR in lung cancer and underscore recent advancements in understanding how TCMs might surmount this form of resistance. The review begins by investigating the unique characteristics of TCMs and their pivotal function in reversing MDR in lung cancer. Subsequently, it explores various forms of MDR in lung cancer, such as aberrant expression of cell membrane transport proteins, dysregulation of intracellular enzyme systems, disrupted apoptosis, and heightened cellular repair mechanisms, emphasizing their detrimental impact on lung cancer treatment outcomes. Central to this review is a thorough analysis of the intricate mechanisms by which TCMs counteract MDR, along with an assessment of their efficacy in lung cancer therapy. Based on this analysis, the review offers insights into potential future research directions for utilizing TCMs to overcome MDR. This review seeks to provide a thorough examination of the role of TCMs in reversing MDR in lung cancer and to stimulate additional research into their clinical applications.

Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment. ELMO domain containing 2 (ELMOD2) is a GTPase-activating protein that regulates a range of cellular biological processes. However, its specific role and prognostic value in tumorigenesis are still unknown. This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.

The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas, elucidating its associations with clinicopathological parameters and patient prognosis. Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and Gene Set Variation Analysis (GSVA) were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis. Specific small interfering RNAs (siRNAs) were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.

ELMOD2 was overexpressed in gliomas, and this upregulation was correlated with tumor grade, isocitrate dehydrogenase mutation, and 1p/19q codeletion status. Notably, ELMOD2 expression was elevated in classical and mesenchymal subtypes, and single-cell resolution analysis revealed predominant enrichment within malignant cells. Functionally, ELMOD2 regulated cell cycle progression, and its overexpression was related to independent adverse outcomes. In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm. Furthermore, ELMOD2 knockdown reduced proliferation, migration, and invasion and increased apoptosis in U251 and A172 cell lines. Finally, ELMOD2 knockdown significantly decreased p-Erk1/2.

ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker. Thus, ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.

Synthetic chloride carriers are known to induce chloride-mediated apoptosis inside cancer cells. One of the main disadvantages is the unfavorable cytotoxicity towards healthy cells due to the lack of selectivity. The use of stimuli, such as light, enzymes, ligands, etc., has enabled the selective activation of these systems in cancer cells. Light, notably, is a significant stimulus that has been utilized due to its excellent spatiotemporal control, remote addressability, and low cytotoxicity. However, previously reported photoresponsive systems require UV radiation for their activation, which has low tissue penetration and can lead to phototoxic cell damage or death. Herein, we report 3-substituted indole-2-carboxamide ion carriers and their o-nitrobenzyl (ONB) linked procarriers. The incorporation of the electron-donating substituents to the ONB photocleavable group leads to a significant red shift in the absorption wavelength, and for the N,N-dimethyl-based procarrier, the absorbance peak extends up to 500 nm. Eventually, all the synthesized procarriers were photoactivated inside MCF-7 cancer cells under 400 nm electromagnetic radiation, and the N,N-dimethyl-based procarrier was also photoactivated at 450 nm. This photoactivation at a higher wavelength of electromagnetic radiation is highly desirable for its practical biological applications.

Breast cancer (BC) is one of the most common malignant tumors in women worldwide, and its treatment faces numerous challenges. Despite the effectiveness of modern treatment methods such as surgery, radiotherapy, chemotherapy, and targeted therapy, issues like recurrence, metastasis, and drug resistance still significantly affect patient prognosis and survival rates. This is particularly true for triple-negative breast cancer (TNBC) and HER2-positive BC, for which treatment outcomes are relatively poor. Withaferin A (WA), a natural plant-derived compound, has shown significant anti-cancer effects in the treatment of BC. WA inhibits the progression of BC through multiple mechanisms, including suppressing cell migration and invasion, inducing tumor cell apoptosis, regulating autophagy and metabolic pathways, and modulating miRNA expression. In combination therapy, WA exhibits a good synergistic effect when used with other anti-cancer drugs such as phenethyl isothiocyanate (PEITC), cisplatin, and sulforaphane, significantly enhancing therapeutic efficacy and reducing drug resistance. This review summarizes the research progress on the mechanisms of WA in combating BC, aiming to provide a foundation for the scientific development and clinical application of WA in BC treatment.

Diet plays a crucial role in cancer development and progression, beyond traditional risk factors. This review aims to summarize current evidence on the role of diet and specific nutrients in cancer development and progression, focusing on molecular mechanisms. We also discuss the potential of personalized dietary interventions, based on tumor and patient characteristics, in enhancing cancer prevention and treatment strategies. The review covers the impact of calories, protein, sugar, and other dietary components on signaling pathways and growth factors involved in carcinogenesis. We examine the influence of obesity, insulin resistance, and other metabolic factors on cancer risk and outcomes. The article also explores current dietary strategies, including calorie restriction, ketogenic diets, and the role of the gut microbiome in modulating response to anticancer therapies. Finally, we highlight the need for further research to develop targeted, personalized dietary recommendations based on an individual's tumor profile, stage of disease, and other clinical factors. Integrating such personalized dietary approaches into cancer prevention and treatment holds promise for improving patient outcomes and quality of life.

Increasing evidence has shown that programmed cell death (PCD) plays a crucial role in tumorigenesis and cancer progression. The components of PCD are complex and include various mechanisms such as apoptosis, necroptosis, alkaliptosis, oxeiptosis, and anoikis, all of which are interrelated in their functions and regulatory pathways. Given the significance of these processes, it is essential to conduct a comprehensive study on PCD to elucidate its multifaceted nature. Key signaling pathways, particularly the caspase signaling pathway, the RIPK1/RIPK3/MLKL pathway, and the mTOR signaling pathway, are pivotal in regulating PCD and influencing tumor progression. In this review, we briefly describe the generation mechanisms of different PCD components and focus on the regulatory mechanisms of these three major signaling pathways within the context of global PCD. Furthermore, we discuss various tumor therapeutic compounds that target different signaling axes of these pathways, which may provide novel strategies for effective tumor therapy and help improve patient outcomes in cancer treatment.

Melanoma is a malignant tumor that originates from activated or genetically altered epidermal melanocytes, resulting from the interplay of genetic, somatic, and environmental factors. It is the fastest-growing malignancy among the Caucasian population and has a high mortality rate, second only to lung cancer. Current mainstream treatments have led to unavoidable drug resistance and toxic side effects despite improvements in efficacy and prognosis. Traditional Chinese Medicine is a significant component of complementary and alternative medicine, playing a vital role in cancer treatment. Natural compounds derived from Chinese herbal medicines offer notable advantages owing to their multimolecular, multitarget, and multipathway characteristics. These compounds exert anti-melanoma effects through various mechanisms, including antiproliferation, promotion of apoptosis, inhibition of metastasis, suppression of angiogenesis, modulation of autophagy, and enhancement of the immune response. Furthermore, combining natural compounds with mainstream antagonistic medicine not only enhances treatment efficacy but also significantly reverses multidrug resistance. This article discusses the specific mechanisms by which natural compounds combat melanoma and reviews the recent research advancements in this field. It also addresses the challenges faced in the widespread clinical application of these natural compounds in melanoma treatment and outlines the future directions for their development.

Neutrophil extracellular traps (NETs), web-like complex structures secreted by neutrophils, have emerged as key players in the modulation of immune responses and the immunopathogenesis of immune disorders. Initially described for their antimicrobial function, NETs now play a part in the fundamental processes of cancer biology, including cancer initiation, metastatic dissemination, and immune evasion strategies. NETs hijack anti-tumor immunity by entrapping circulating cancer cells, fostering the growth of tumors, and reorganizing the tumor microenvironment such that it is pro-malignancy. Emerging evidence emphasizes the role of NETosis coupled with non-coding RNAs-long non-coding RNAs (lncRNAs) and microRNAs (miRNAs)-as key regulators of gene expression and controllers of processes vital for cancer growth, such as immune response and programmed cell death processes like apoptosis, necroptosis, pyroptosis, and ferroptosis. Aberrantly expressed non-coding RNAs have been attributed to immune dysregulation and excessive NET production, promoting tumor growth. NETs are also associated with a myriad of pathological conditions, such as autoimmune disorders, cystic fibrosis, sepsis, and thrombotic disorders. New therapeutic approaches-such as DNase therapy and PAD4 inhibitors-target NET production and their degradation to modify immune function and the efficiency of immunotherapies. Further clarification of the intricate interactions of NETosis, lncRNAs, and miRNAs has the potential to establish new strategies for the suppression of the growth of tumors and preventing immune evasion. This review seeks to elucidate the interactions between NETosis and the regulatory networks involving non-coding RNAs that significantly contribute to the immunopathogenesis of cancer.

Transfer of extracellular and intracellular calcium ions (Ca2⁺) plays a crucial role in programmed cell death, with varied Ca2⁺ concentrations associated with cell growth, proliferation, apoptosis, and so on. Real-time monitoring of extracellular Ca2⁺ concentrations ([Ca2+]e) can provide valuable quantitative insights into programmed cell death, which may greatly benefit cancer therapy and other biological applications. This study used a modified ion-sensitive field-effect transistor (ISFET) as a platform for Ca2⁺ sensing. The ISFET device was functionalized with a Ca2⁺-selective membrane containing polyurethane (PU) and calcium ionophore II. The Ca2⁺-FET device exhibited a sensitivity of 35 ± 3 mV/pCa (pCa 0-5) toward Ca2⁺ with insignificant cross-sensitivity to other ions, such as sodium (Na⁺) and potassium (K⁺). The device was applied to monitor [Ca2+]e concentrations in the MDA-MB-231 breast cancer cell culture, showing sufficient reliance in detecting Ca2⁺ concentrations (0.1 mM to 1 M (pCa 0-5)) correlated with cellular activities. This technique offers a noninvasive and label-free approach for real-time Ca2⁺ monitoring in cell culture, with potential applications in cancer research and therapeutic development.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by KIT or PDGFRA mutations. Programmed cell death (PCD), including apoptosis, autophagy, and ferroptosis, plays a crucial role in GIST pathogenesis, progression, and treatment response. Non-coding RNAs (ncRNAs) have emerged as key regulators of PCD pathways, influencing GIST proliferation, metastasis, and drug resistance, particularly in response to tyrosine kinase inhibitors (TKIs) such as imatinib. Apoptosis suppression is strongly associated with poor prognosis, while autophagy contributes to tumor dormancy and TKI resistance. Ferroptosis, a novel iron-dependent cell death pathway, represents a promising therapeutic target. Recent evidence suggests that ncRNAs modulate these PCD pathways through interactions with key molecular regulators such as miR-494, miR-30a, and lncRNAs, which affect signaling networks including PI3K/AKT, MAPK, and mTOR. Furthermore, ncRNAs have mediated secondary resistance to imatinib by promoting autophagic flux and altering ferroptosis sensitivity. Understanding the molecular interplay between ncRNAs and PCD in GIST provides novel insights into disease mechanisms and offers potential therapeutic strategies to overcome drug resistance. Targeting ncRNA-mediated regulation of apoptosis, autophagy, and ferroptosis may enhance treatment efficacy and improve patient outcomes. Future research should focus on elucidating the mechanistic roles of ncRNAs in PCD pathways to develop innovative diagnostic and therapeutic approaches for GIST.

Sertoli cell-only (SCO) tubules are a histologic pattern characterized by the absence of germ cells within seminiferous tubules, leading to infertility in both humans and dogs. While its association with testicular tumors has been documented, the role of iron metabolism in SCO tubules remains unclear. This study investigates the immunolabeling of key iron-related proteins (Transferrin Receptor 1, Transferrin Receptor 2, and Ferritin Heavy chain 1) and Proliferating Cell Nuclear Antigen (PCNA) in canine SCO tubules within distinct microenvironments: seminomas, Sertoli cell tumors, and isolated. We confirm the presence and distribution of iron-related proteins in Sertoli cells as a part of a Sertoli cell-only pattern across different microenvironments. Our findings suggest a potential increase in iron uptake in association with tumors, and the cytoplasmic PCNA immunolabeling suggests a preferential activation of cell survival rather than proliferation, potentially facilitating neoplastic transformation. In contrast, Sertoli cells in the isolated Sertoli cell-only pattern exhibit nuclear PCNA immunolabeling, possibly correlated to the state of immaturity of Sertoli cells. These findings highlight the role of iron homeostasis and apoptosis in testicular tumorigenesis. Immunohistochemistry revealed that Sertoli cells in SCO tubules actively uptake iron in all conditions, yet their capacity to utilize it for proliferation appears restricted. Interestingly, PCNA labeling exhibits a pattern dependent on the microenvironment: in tumor-associated SCO tubules, it showed cytoplasmic localization, characteristic of an anti-apoptotic function, whereas isolated SCO tubules showed nuclear PCNA labeling, suggesting a potential role in DNA synthesis and repair. These findings highlight the interplay between iron homeostasis and cellular survival mechanisms, offering novel perspectives on its pathophysiology and implications for testicular cancer development.

Cervical cancer (CC) is a prevalent malignant tumor in the female reproductive system, with rising incidence rates among younger women posing a significant public health challenge. Human papillomavirus (HPV) infection is the primary cause, driving carcinogenesis by promoting abnormal proliferation of tumor cells. Ferroptosis is a form of regulated necrosis that is caused by an iron-dependent accumulation of lipid peroxides with rupture of the plasma membrane. Targeting ferroptosis-related molecules and pathways can selectively induce cervical cancer cell death, while alterations in the expression of ferroptosis-related genes provide promising biomarkers for prognostic assessment. Advances in research on biomarkers and molecular targets are improving predictions of therapeutic outcomes, overcoming drug resistance, and optimizing immunotherapy strategies, thereby opening new avenues for precision medicine. This review focuses on the molecular mechanisms underlying ferroptosis in cervical cancer, discusses its potential applications in early diagnosis and prognosis evaluation, and summarizes the latest advancements in targeted therapy, aiming to provide a novel perspective for the clinical management of cervical cancer.

Glufosinate-ammonium (GLA) is a widely used organophosphorus herbicide, which poses a potential threat to non-target aquatic species. This study aimed to evaluate the toxic effects of acute exposure to GLA on the hepatopancreas of juvenile Eriocheir sinensis, and to preliminarily reveal the toxicity mechanism. The results showed that the 96h-LC50 of GLA on juvenile E. sinensis was 386.61 mg/L. The acute test showed that GLA exposure caused hepatopancreas histological lesions, DNA damage and a higher apoptosis rate. The activities of aspartate aminotransferase and alanine aminotransferase in serum increased significantly and had a concentration-dependent effect. Moreover, GLA exposure resulted in a significant increase in malondialdehyde content, which subsequently activated the antioxidant system and detoxification system, and the related enzyme activities and gene expression levels were significantly increased. In addition, the RNA-Seq analysis showed that the toxic effects of GLA exposure on juvenile crabs may mainly involve physiological pathways such as energy metabolism, protein synthesis and nervous system function. This study highlights the hepatotoxic effects of GLA on aquatic crustaceans and preliminarily reveals the key pathways of action. The results of this study will helpful to provide new insights into the toxic effects and risk assessment of herbicides on non-target organisms.

The traditional medicinal plant Centella asiatica is commonly used in Chinese and Ayurvedic medicine due to its vast range of therapeutic properties. Previously, the ethanolic C. asiatica leaf extract was subjected to silica column fractionation, and the C3 fraction was obtained. We investigated the antioxidant and anti-proliferative effects of C3 in human embryonic kidney (HEK293) cells. In HEK293 cells, C3 cytotoxicity was assessed (viability assay; 24 h; [0.2-3 mg/mL]), and a half maximal inhibitory concentration (IC50) was determined. Malondialdehyde (MDA), lactate dehydrogenase (LDH) (spectrophotometry), mitochondrial depolarization (Δψm), intracellular reactive oxygen species (flow cytometry), glutathione (GSH), oxidized glutathione (GSSG) concentrations, caspase activities, ATP levels (luminometry), and fragmentation of DNA (SCGE assay) were evaluated. Protein expressions were assessed by western blotting. Gene expressions were quantified by qPCR. Cell viability in HEK293 cells was decreased in a dose-dependent manner by C3. MDA, Δψm, LDH, caspase activities, and DNA fragmentation (P < .0004) were significantly increased by C3. Nuclear factor erythroid 2-related factor 2 (Nrf-2) protein expression, GSH, and GSSG concentrations were increased, whereas antioxidant (Nrf-2, GPx, SOD, and CAT) gene expression was significantly decreased by C3 (P < .001). C3 decreased both Bax and Bcl-2 protein expression (P < .03). Gene expression of c-myc was significantly increased, whereas OGG-1 was significantly reduced by C3 (P < .05). C3 reduced antioxidant gene expression, increased antioxidant levels, and elevated anti-proliferative effects in HEK293 cells, suggesting that high concentrations of C3 are potentially toxic to kidney cells, thus rendering cause for concern with its human use.

Colon cancer (CC) ranks is the second leading cause of cancer-related deaths globally. Despite chemotherapy being a primary treatment its effectiveness significantly declines in advanced in stage. Emerging evidence suggests that dietary components particularly polysaccharides, play a role in CC progression. This study employed multi-omics and network pharmacology to elucidate the mechanisms underlying the apoptotic effects of Caulerpa lentillifera polysaccharide (CLP) in CC, validated through in vitro and in vivo experiments. Transcriptomics and network pharmacology analysis identified the p53/Bax/Caspase-3 pathway as a key regulatory axis. Further targeted analysis of amino acid metabolism revealed that CLP significantly decreased intracellular aspartate (Asp) levels. Additionally, reactive oxygen species (ROS) accumulation was detected in cells. CLP treatment reduced Asp content, leading to ROS accumulation, which activated the p53/Bax/Caspase-3 pathway, triggering apoptosis. In vivo, CLP effectively inhibited tumor growth in BALB/c mice bearing CT26 colon cancer cells. These findings suggest that CLP exerts anti-colon cancer effects by modulating amino acid metabolism and inducing apoptosis via the p53/Bax/Caspase-3 axis, providing a promising therapeutic strategy for CC.

Autophagy, an evolutionarily conserved process, plays an important role in cellular homeostasis and human diseases. Cardiovascular dysfunction, which presents during cancer treatment or in cancer-free individuals years after treatment, is a growing clinical challenge. Millions of cancer survivors and patients face an unpredictable risk of developing cardiotoxicity. Cardiotoxicity due to cancer treatment, as well as cancer progression, has been linked to autophagy dysregulation. Modulating autophagy has been further proposed as a therapeutic treatment for both cancer and cardiovascular disorders. The safe and effective use of autophagy modulation as a cardioprotective strategy during cancer treatment especially requires careful consideration and experimentation to minimize the impact on cancer treatment. We focus here on recent advances in targeted autophagy modulation strategies that utilize interdisciplinary approaches in biomedical sciences and are potentially translatable to treat cardiotoxicity and improve cancer treatment outcomes. This review highlights non-small molecule autophagy modulators to enhance targeted therapy, nanomedicine for autophagy modulation and monitoring, and in vitro models and future experiments needed to bring novel autophagy discoveries from basic research to clinical translation.

Background/Objectives: Lercanidipine is a third-generation dihydropyridine calcium channel blocker. In addition to their well-established cardiovascular effects, calcium channel blockers are increasingly recognized for their therapeutic potential in various cancers. This study aimed to investigate the potential anticancer effects of lercanidipine on cancer cell lines-particularly in combination with cisplatin-by assessing parameters such as cell viability (MTT assay), proliferation, MAPK pathway activity, caspase enzyme levels, and TNF-α expression. Methods: In this study, the effects of lercanidipine, both alone and in combination with cisplatin, on cell viability were evaluated using the MTT assay in MCF-7, SH-SY5Y, PC3, and HEK293 cell lines. To assess intracellular signaling and apoptotic pathways, MAPK inhibition, as well as caspase-3 and caspase-8 activities, were measured using ELISA. Additionally, to evaluate the anti-inflammatory potential, TNF-α levels in LPS-stimulated RAW264.7 cells were analyzed via. Results: The study revealed that lercanidipine showed significant cytotoxic effects, particularly in SH-SY5Y and PC3 cancer cell lines, while it did not induce a 50% loss of viability in healthy HEK293 cells. When combined with cisplatin, lercanidipine enhanced cytotoxicity by 2.7-fold in neuroblastoma (SH-SY5Y) cells, 1.6-fold in breast cancer (MCF7) cells, and 1.9-fold in prostate cancer (PC3) cells. MAPK activity was inhibited by 83.6% at 20 μM lercanidipine, while dose-dependent increases in caspase-3 and caspase-8 activities were observed. Additionally, lercanidipine decreased TNF-α levels in LPS-stimulated RAW264.7 cells, indicating its potential anti-inflammatory effect. Conclusions: In conclusion, lercanidipine demonstrated selective anticancer effects in cancer cell lines and showed synergistic cytotoxicity when combined with cisplatin. It also significantly inhibited MAPK signaling, activated apoptotic caspases, and reduced TNF-α levels, suggesting potential anti-inflammatory activity. These findings highlight lercanidipine's potential for repurposing as an adjunct in cancer therapy.

Heat shock factor 1 (HSF1) is the master orchestrator of the heat shock response (HSR), a critical process for maintaining cellular health and protein homeostasis. These effects are achieved through rapid expression of molecular chaperones, the heat shock proteins (HSPs), which ensure correct protein folding, repair, degradation and stabilization of multiprotein complexes. In addition to its role in the HSR, HSF1 influences the cell cycle, including processes such as S phase progression and regulation of the p53 pathway, highlighting its importance in cellular protein synthesis and division. While HSF1 activity offers neuroprotective benefits in neurodegenerative diseases, its proteome-stabilizing function may also reinforce tumorigenic transformation. HSF1 overexpression in many types of cancer reportedly enhances cell growth enables survival, alters metabolism, weakens immune response and promotes angiogenesis or epithelial-mesenchymal transition (EMT) as these cells enter a form of "HSF1 addiction". Furthermore, the client proteins of HSF1-regulated chaperones, particularly Hsp90, include numerous key players in classical tumorigenic pathways. HSF1 thus presents a promising therapeutic target for cancer treatment, potentially in combination with HSP inhibitors to alleviate typical initiation of HSR upon their use.

Caspase-independent cell death (CICD) has recently become a very important mechanism in lung cancer, in particular, to overcome a critical failure in apoptotic cell death that is common to disease progression and treatment failures. The pathways involved in CICD span from necroptosis, ferroptosis, mitochondrial dysfunction, and autophagy-mediated cell death. Its potential therapeutic applications have been recently highlighted. Glutathione peroxidase 4 (GPX4) inhibition-driven ferroptosis has overcome drug resistance in non-small cell lung cancer (NSCLC). In addition, necroptosis involving RIPK1 and RIPK3 causes tumor cell death and modulation of immune responses in the tumor microenvironment (TME). Mitochondrial pathways are critical for CICD through modulation of metabolic and redox homeostasis. Ferroptosis is amplified by mitochondrial reactive oxygen species (ROS) and lipid peroxidation in lung cancer cells, and mitochondrial depolarization induces oxidative stress and leads to cell death. In addition, mitochondria-mediated autophagy, or mitophagy, results in the clearance of damaged organelles under stress conditions, while this function is also linked to CICD when dysregulated. The role of cell death through autophagy regulated by ATG proteins and PI3K/AKT/mTOR pathway is dual: to suppress tumor and to sensitize cells to therapy. A promising approach to enhancing therapeutic outcomes involves targeting mechanisms of CICD, including inducing ferroptosis by SLC7A11 inhibition, modulating mitochondrial ROS generation, or combining inhibition of autophagy with chemotherapy. Here, we review the molecular underpinnings of CICD, particularly on mitochondrial pathways and their potential to transform lung cancer treatment.

Cancer, uncontrolled cell growth due to the loss of cell cycle regulation, is often found to be associated with viral infections and, as recent studies show, with bacterial infections as well. Emerging reports also suggest a strong link between fungi and cancer. The crucial virulence trait of fungi, the switch from yeast (Y) to hyphal (H) form, is found to be associated with carcinogenesis. The physicochemical properties and signal transduction pathways involved in the switch to the hyphal form overlap with those of tumor cell formation. Inhibiting differentiation causes apoptosis in fungi, whereas preventing apoptosis leads to cancer in multicellular organisms. Literature on the fungi-cancer linkage, though limited, is increasing rapidly. This review examines cancer-specific fungal communities, the impact of fungal microbiome on cancer cell progression, similarities between fungal differentiation and cells turning cancerous at biochemical and molecular levels, including the overlaps in signal transduction pathways between fungi and cancer. Based on the available evidence, we suggest that molecules inhibiting the yeast-hyphal transition in fungi can be combined with those targeting tumor cell apoptosis for effective cancer treatment. The review points out fertile research areas where mycologists and cancer researchers can collaborate to unravel common molecular mechanisms. Moreover, antibodies targeting fungal-specific chitin and glucan can be used for the selective neutralization of tumor cells. These new combinations of potential therapies are expected to facilitate the development of target-specific, less harmful and commercially feasible anticancer therapies. We bring together available evidence to argue that fungal infections could either trigger cancer or have a significant role in the development and progression of cancer. Hence, cancer-associated fungal populations could be utilized as a target for a combination therapy involving the integration of anticancer and antifungal drugs as well as inhibitors of fungal morphogenesis to develop more effective anticancer therapies.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. The difficulty in early diagnosis, combined with the tendency for tumor invasion and metastasis, creates significant challenges for current therapeutic approaches. Additionally, the pharmaceutical agents currently used to treat NSCLC often come with severe side effects and can lead to drug resistance. As a result, there is an urgent need to develop new therapeutic agents with fewer side effects that can effectively overcome resistance mechanisms. Flavonoids, a prominent class of natural compounds, have shown promise in preventing and treating various cancers. By structurally optimizing flavonoids, it is possible to enhance their anticancer activity and improve their pharmacokinetic properties. This article reviews the different mechanisms of action and structure-activity relationships (SARs) of flavonoid derivatives in treating NSCLC, aiming to provide a scientific foundation for developing new therapeutic agents.

Infections caused by non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus, elicit diverse cell death mechanisms including apoptosis, necrosis, and pyroptosis, which play key roles in immunopathogenesis. NTM can manipulate these cell death pathways to evade host immune responses, ensuring their intracellular survival and persistence. Apoptosis may aid in antigen presentation and immune activation, while necrosis and pyroptosis trigger excessive inflammation, leading to tissue damage. Autophagy, a crucial cellular defense mechanism, is often induced in response to NTM infection; however, M. abscessus has evolved mechanisms to inhibit autophagic processes, enhancing its ability to survive within host cells. This manipulation of cell death pathways, particularly the dysregulation of autophagy and ferroptosis, contributes to chronic infection, immune evasion, and tissue damage, complicating disease management. Understanding these mechanisms offers potential therapeutic targets for improving treatment strategies against M. abscessus infections.

Novel lipophilic cationic derivatives including quaternary ammonium salt and triphenylphosphine series were designed and synthesized using diosgenin (1) and sarsasapogenin (2) as substrates to improve the cytotoxicity and selectivity. Most of the derivatives showed higher cytotoxicity against all cancer cell lines tested, compound 13 exhibited the most superior activity against A549 cells with an IC50 value of 0.95 μM, which was 34-fold of diosgenin. Preliminary cellular mechanism studies elucidated that compound 13 might arrest cell cycle at G0/G1 phase, trigger apoptosis via up-regulating the expression of Bax, down-regulating the expression of Bcl-2 and caspase-3, and induce an increase in the generation of intracellular reactive oxygen species (ROS) in A549 cells. In addition, molecular docking analysis revealed that compound 13 could occupy the active site of p38α-MAPK well and interact to the surrounding amino acids by salt bridge and conjugation. These results suggested that compound 13 had the potential to serve as an antitumor lead agent, probably exert antitumor effect through mitochondrial pathway and p38α MAPK pathway.

Esophageal cancer (ESCA) is among the most prevalent and lethal tumors globally. While nitric oxide synthase 1 (NOS1) is recognized for its important involvement in various cancers, its specific function in ESCA remains unclear.

To explore the potential role and underlying mechanisms of NOS1 in ESCA.

Survival rates were analyzed using GeneCards and Gene Expression Profiling Interactive Analysis. The effects and mechanisms of NOS1 on ESCA cells were evaluated via the Cell Counting Kit-8 assay, scratch assay, Transwell assay, flow cytometry, quantitative polymerase chain reaction, western blotting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. The protein interaction network was used to screen the interacting proteins of NOS1 and validate these interactions through co-immunoprecipitation and dual luciferase assays. Additionally, a nude mouse xenograft model was established to evaluate the effect of NOS1 in vivo.

The survival rate of patients with ESCA with high NOS1 expression was higher than that of patients with low NOS1 expression. NOS1 expression in ESCA cell lines was lower than that in normal esophageal epithelial cells. Overexpression of NOS1 (oe-NOS1) inhibited proliferation, invasion, and migration abilities in ESCA cell lines, resulting in decreased autophagy levels and increased apoptosis, pyroptosis, and ferroptosis. Protein interaction studies confirmed the interaction between NOS1 and NOS1 adaptor protein (NOS1AP). Following oe-NOS1 and the silencing of NOS1AP, levels of P62 and microtubule-associated protein 1 light chain 3 beta increased both in vitro and in vivo. Furthermore, the expression levels of E-cadherin, along with the activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT), were inhibited in ESCA cell lines.

NOS1 and NOS1 proteins interact to suppress autophagy, activate the PI3K/AKT pathway, and exert anti-cancer effects in ESCA.

PANoptosis, a complex programmed cell death (PCD) pathway that includes apoptosis, pyroptosis and necroptosis, is significantly involved in the progression of cancers. Long noncoding RNAs (lncRNAs) play crucial roles in PCD. However, the predictive value of PANoptosis-related lncRNAs (PRlncRNAs) for colon adenocarcinoma (COAD) has not been established.

Gene expression data and clinical characteristics of patients with COAD were obtained from The Cancer Genome Atlas database. Differential expression analysis and Pearson correlation analysis were used to identify PRlncRNAs. In addition to least absolute shrinkage and selection operator, univariate and multivariate Cox regression analyses were employed to obtain PRlncRNAs for constructing a risk signature. Patients with COAD in the training set, testing set and entire set were stratified into high- and low-risk groups for further comparison of survival prognosis, using the median risk score as the cut-off point. Time-dependent receiver operating characteristic curves, a nomogram and multivariate Cox regression analysis were conducted to validate the risk signature in the testing set and the entire set. In addition, critical pathways, immune infiltration cells, immune checkpoint-related genes, Tumor Immune Dysfunction and Exclusion (TIDE) scores and antitumour drugs were compared between the two risk groups in the entire set. Correlations between ferroptosis, cuproptosis, disulfidptosis and the PRlncRNA risk score were evaluated. Finally, a competitive endogenous RNA (ceRNA) network was established, and enrichment analysis of the predicted mRNAs was performed using Gene Ontology (GO) analysis. The Kaplan-Meier plotter database was used as an external database to confirm the accuracy of the risk signature in predicting patient prognosis. Additionally, small interfering RNA (siRNA), a cell counting kit- 8 assay, a cell colony formation assay, quantitative polymerase chain reaction (qPCR) and an apoptosis assay were further employed to investigate the roles of AP003555.1 in colon cancer.

A risk signature comprising four PRlncRNAs (LINC01133, FOXD3-AS1, AP001066.1, and AP003555.1) was developed to predict the prognosis of patients with COAD. Kaplan‒Meier curves demonstrated significant differences in prognosis between the high- and low-risk groups across the three sets. Multivariate Cox regression analysis confirmed that the risk signature was an independent prognostic factor across the three sets. A nomogram, receiver operating characteristic curves and calibration curves indicated strong confidence in the risk signature. Using the CIBERSORT algorithm and gene set enrichment analysis, variations in infiltrating immune cells and immune processes were observed between the two risk groups. Furthermore, TIDE algorithm suggested that the high-risk group exhibited a lower risk of immunotherapy escape and better immunotherapy outcomes than the low-risk group. Distinct responses to various antitumour drugs were observed between the two risk groups. Additionally, we constructed a ceRNA network based on PRlncRNAs, and GO enrichment analysis of the predicted mRNAs revealed different functions. In addition, the results of the Kaplan‒Meier plotter database revealed that patients who exhibited high levels of LINC01133 and FOXD3-AS1 experienced significantly shorter overall survival than those with low levels of these lncRNAs. Specifically, in terms of functionality, AP003555.1 was found to be highly expressed in colon cancer tissue and promoted viability and proliferation while suppressing the apoptosis of colon cancer cells.

We identified a novel risk signature consisting of four PRlncRNAs, which is an independent prognostic indicator for patients with COAD. This PRlncRNA risk signature is potentially relevant for immunotherapy and could serve as a therapeutic target for COAD.

Immunogenic cell death (ICD) has attracted enormous attention over the past decade due to its unique characteristics in cancer cell death and its role in activating innate and adaptive immune responses against tumours. Many efforts have been dedicated to screening, identifying and discovering ICD inducers, resulting in the validation of several based on metal complexes. In this review, we provide a comprehensive summary of current metal-based ICD inducers, their molecular mechanisms for triggering ICD initiation and subsequent protective antitumour immune responses, along with considerations for validating ICD both in vitro and in vivo. We also aim to offer insights into the future development of metal complexes with enhanced ICD-inducing properties and their applications in potentiating antitumour immunity.

Lymphoma is a common cancer of the lymphatic system, and its treatment presents considerable clinical difficulties due to the constraints of existing medicines. Anticancer drug such as Doxorubicin (DOX) is an effective chemotherapeutic drug that is frequently used to treat lymphoma and other cancers; however, it is linked with considerable toxicities. Fisetin, a naturally occurring flavonoid, exhibits anticancer properties and has the potential to augment the therapeutic effects of DOX. This study explores the synergistic effects of combining DOX with fisetin in the treatment of lymphoma. The combination of DOX and fisetin significantly inhibits cell viability, induced membrane blabbing, chromatin condensation, and promoted apoptosis compared to monotherapies. The study also showed that the synergistic effect of fisetin along with DOX significantly promotes apoptosis in DL cells through intracellular ROS generation, mitochondrial aggregation at the periphery of the nucleus and, increased p53, Bax, cytochrome c, caspase 3, caspase 9, and cleaved caspase 9 expression. Additionally, combination therapy not only increased the mean survival of the treated group animals but also reduced the tumor burden. While histopathological parameters have shown overall improvement in combination therapy. This study proposes a novel combinational therapy for the treatment of lymphoma and requires further clinical investigation.

Viewing the hallmarks as a sequence of adaptations captures the "why" behind the "how" of the molecular changes driving cancer. This eco-evolutionary view distils the complexity of cancer progression into logical steps, providing a framework for understanding all existing and emerging hallmarks of cancer and developing therapeutic interventions.

Drug resistance in cancer poses a serious challenge in finding an effective remedy for cancer patients, because of the multitude of contributing factors influencing this complex phenomenon. One way to counter this problem is using a more targeted and dose-limiting approach for drug delivery, rather than relying on conventional therapies that exhibit multiple pernicious side-effects. Stability and specificity have traditionally been the core issues of peptide-based delivery vectors. In this study, we employed a structural regression modelling approach in the design, synthesis and characterization of a series of peptides that belong to approximately same topological cluster, yet with different electrostatic signatures encoded as a result of their differential positioning of amino acids in a given sequence. The peptides tagged with the fluorophore 5(6)-carboxyfluorescein, showed higher uptake in cancer cells with some of them colocalizing in the lysosomes. The peptides tagged with the anti-cancer drug methotrexate have displayed enhanced cytotoxicity and inducing apoptosis in triple-negative breast cancer cells. They also showed comparable uptake in side-population cells of lung cancer with stem-cell like properties. The most-optimized peptide showed accumulation in the tumor resulting in significant reduction of tumor size, compared to the untreated mice in in-vivo studies. Our results point to the following directives; (i) peptides can be design engineered for targeted delivery (ii) stereochemical engineering of peptide main chain can resist proteolytic enzymes and (iii) cellular penetration of peptides into cancer cells can be modulated by varying their electrostatic signatures.