Resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) poses a significant challenge to enhancing the efficacy of cancer treatments. Beyond the cellular mechanisms intrinsic to tumor cells, the modulation of the tumor immune microenvironment is crucial in dictating the responsiveness to pharmacological interventions. Thus, there is a pressing need to elucidate the intricate interplay between PARPi and antitumor immune responses and to develop an optimized combinatorial therapeutic approach. In this study, using matched tumor samples before and after neoadjuvant monotherapy with the PARPi niraparib in a prospective clinical trial (NCT04507841), we observed a significant increase in natural killer (NK) cell infiltration post-treatment. However, this was not accompanied by the expected enhancement in their cytotoxic functions. This observation underscores the necessity to optimize the antitumor potential of NK cells by enhancing their cytotoxic capabilities. Upon exposure to niraparib, tumor cells, particularly those with wild-type EGFR, exhibited a pronounced upregulation of human leukocyte antigen G (HLA-G), an immune checkpoint impeding NK cell functions. Niraparib promotes EGFR internalization, which in turn diminishes AKT/mTOR signaling, leading to the increased transcriptional activity of the transcription factor EB (TFEB) and subsequent enhancement of HLA-G expression. The combination of niraparib with HLA-G blockade not only augmented NK cell-mediated tumor lysis in vitro but also synergistically inhibited tumor growth in humanized patient-derived xenograft models. Collectively, our results shed light on a previously unrecognized immune evasion mechanism and offer a compelling argument for the integration of HLA-G blockade with PARPi in cancer therapy.

Non-small cell lung cancer (NSCLC) is still the leading cause of lung cancer-related deaths globally, affecting both men and women. Mutations in the epidermal growth factor receptor (EGFR) are most common among patients with NSCLC, especially Asian patients. Here, we introduce an electrochemical capacitive biosensor for the early detection of NSCLC through specific identification of EGFR. A novel and reagentless EGFR aptamer was designed using the systematic evolution of ligands by exponential enrichment (SELEX) process and immobilized on a chromium (Cr)/gold (Au) electrode, with capacitance signals used for detection. The biosensor employs an interdigitated capacitor electrode (IDCE) functionalized with 3-mercaptopropionic acid (MPA), enhancing EGFR aptamer immobilization, while 6-mercapto-1-hexanol (MCH) was used for effective blocking to ensure robust and high-affinity binding to target analytes. The IDCE capacitive biosensor achieved real-time rapid detection within 3 s and demonstrated a detection limit of 0.005 ng/mL for the EGFR peptide, with a dynamic range of 10-11-10-7 ng/mL. Furthermore, the specific EGFR aptamer-immobilized IDCE biosensor was found to be regenerable and reusable up to five times using deionized water. This biosensor offers a rapid, label-free, and highly selective approach for early-stage EGFR detection in NSCLC. Its portability and scalability make it a promising tool for point-of-care diagnostic applications in biomedicine, potentially advancing the field of cancer diagnostics.

Six series of 2,4,6,7-tetrasubstituted quinazolines 4a-c, 6a-c, 8a-c, 10a-d, 13a-d along with quinazoline-tetrahydropyrimidine hybrids 15a-c were designed and synthesized based on keeping the essential key binding pattern of some EGFR inhibitors to appraise their EGFR inhibition and anticancer activity. Twelve compounds out of twenty displayed a significant EGFR inhibition in a subnanomolar level (IC50 = 0.143-0.946 nM) compared to afatinib (IC50 = 0.102 nM). The most potent derivatives 4a, 6c, 8b, 13a and 15b (IC50 = 0.143-0.313 nM) were further screened for their anticancer activity against lung (A549) and colon (HCT116) cancer cell lines, in addition to, normal fibroblast cells (WI-38). It was found that, compounds 6c and 13a show a nearly equipotent to superior cytotoxicity towards (A549) (IC50 = 0.020 and 0.006 μM; respectively) and (IC50 = 0.020 and 0.038 μM; respectively) against HCT116 in comparison to afatinib (IC50 = 0.025 and 0.030 μM; respectively). Also, compounds 6c and 13a caused a cell cycle arrest at S phase and induced apoptosis in A549 and HCT116; respectively. Moreover, in silico studies clarified the binding pattern of the potent compounds in EGFR enzyme active site and confirmed their ability to gratify the structural features meted for binding and rationalized their selectivity. Furthermore, the most active candidates possess promising predicted pharmacokinetic properties.

Clinical outcomes remain unsatisfactory in patients with pancreatic cancer (PAC). In this study, through single-cell sequencing, we identified eight cell subpopulations in the tumor microenvironment (TME). Redimensional clustering of epithelial cells, myeloid cells, and cancer-associated fibroblasts (CAFs) revealed heterogeneity in the TME of PAC. Intercellular communication analysis showed strong direct interactions between matrix CAFs, inflammatory CAFs, and epithelial cells. Additionally, we found that the SPP1-associated pathway was activated in monocytes, whereas the vascular endothelial growth factor-associated pathway was activated in epithelial cells. These results improve the understanding of the TME of pancreatic cancer and provide a foundation for further studies on intratumoral heterogeneity. In addition, differentially expressed gene secretory leukocyte protease inhibitor (SLPI) was identified in pancreatic cancer, and functional experiments showed that SLPI had a strong impact on cell viability and apoptosis, which offers a potential therapy target for pancreatic cancer.

Cancer stands as a leading cause of mortality globally. The main female-related malignancies are breast cancer, with 2.3 million new cases annually, and ovarian cancer, with 300,000 new cases per year worldwide. The current treatments like surgery, chemotherapy, and radiation therapy have presumably had deficiencies in sustaining long-term anti-tumor responses. Cellular immunotherapy, also referred to as adoptive cell therapy, has shown encouraging advances by employing genetically modified immune cells in fighting cancer by engineering chimeric antigen receptors (CARs) mainly on T cells and natural killer (NK) cells. Studies in NK cell therapies involve unmodified NK cells and CAR-NK cell therapies, targeting cancer cells while limiting the destruction of normal cells. CAR-NK cells represent the next generation of therapeutic immune cells that have been shown to eliminate malignancies through CAR-dependent and CAR-independent mechanisms. They also represent possible candidates for "off-the-shelf" therapies due to their advantages, including the ability to target cancer cells independently of the major histocompatibility complex, reduced risk of alloreactivity, and fewer severe toxicities compared to CAR-T cells. To date, there have been no comprehensive review studies examining the therapeutic potential of CAR-NK cell therapy specifically for female-related malignancies, such as breast and ovarian cancers. This review offers a thorough exploration of CAR-NK cell therapy in relation to these cancers and their responses to treatment.

Studying the relationship among protein structure, dynamics, and function under external compressive forces offers valuable insights. While extensive research has focused on manipulating protein dynamics and ligand-receptor interactions under pulling forces, the exploration of protein conformational changes under compressive forces has been limited. In this study, we investigate the response of unliganded epidermal growth factor receptor (EGFR) monomers, liganded EGF-EGFR monomers, and dimers when exposed to external compressive forces using a home-modified AFM setup with an ultrasoft AFM tip. We observed that both ligand-bound and unbound EGFR proteins can undergo spontaneous tertiary structural rupture under piconewton-level compressive forces, a previously hidden protein behavior that may play a significant role in protein cell signaling. The magnitudes of the threshold compressive forces obtained in our study lie in the range of tens and hundreds of piconewtons (pN), which is accessible within a live biological system. Moreover, we developed a kinetic model to exhibit that only a fraction of the uniaxial compressive force exerted by the AFM tip affects the internal tension that causes a pseudopulling force within the protein before it undergoes the tertiary structural rupture. This calculated fraction ranged from 0.45 to 0.65, depending on the protein type and the approach velocity of the AFM tip. Additionally, we employed molecular dynamics (MD) simulations, particularly Steered MD (SMD) simulations along with Umbrella Sampling (US), to investigate the dynamics of unliganded and liganded EGFR in the presence of external compressive forces. These MD simulation results offer valuable insights into the flexibilities and unfolding behaviors of both liganded and unliganded EGFR proteins when subjected to external compressive forces.

Epidermal growth factor receptor (EGFR) mutations represent targetable alterations in non-small cell lung cancer (NSCLC). The treatment landscape in the frontline setting for patients with advanced EGFR-mutated NSCLC is evolving with increasing treatment options. EGFR tyrosine kinase inhibitors (TKIs) have significantly improved outcomes, but resistance inevitably develops, necessitating alternative strategies.

Patritumab deruxtecan is a novel antibody-drug conjugate targeted human epidermal growth factor receptor-3 (HER3), delivering a topoisomerase-I inhibitor payload to HER3-expressing cancer cells. Phase I and II studies have demonstrated efficacy in patients with EGFR-mutant NSCLC with disease progression after prior therapies, including third-generation EGFR TKIs and platinum-based chemotherapy. The phase-II trial reported an objective response rate of 39% and a median progression-free survival of 5.5 months. Patritumab deruxtecan is associated with notable toxicities, including grade 3 and higher hematologic adverse events, gastrointestinal toxicity, and interstitial lung disease (ILD). ILD occurred in 5.3% of patients in the Phase-II study. Early detection and management are crucial for minimizing the risk of complications.

Patients with advanced EGFR-mutant NSCLC who have received TKI therapy and chemotherapy have limited treatment options. Patritumab deruxtecan demonstrates clinical activity in this population with manageable side effects, addressing an unmet need for patients.

Lung cancer poses a significant global burden with rising morbidity and mortality. Coal tar pitch-induced lung cancer is an occupational disease where early detection is crucial but challenging due to unclear pathogenesis. We established a malignant transformation model using BEAS-2B cells treated with coal tar pitch extract (CTPE). Macro- and micro-observations showed CTPE-induced alterations, including changes in cell morphology, enhanced proliferation and migration abilities, upregulated EGFR expression, modified levels of CYP1A1 and GSTM1 metabolizing enzymes, and a transition towards a mesenchymal phenotype. These findings strongly suggest that the cells have undergone malignant transformation. Metabolomics analysis revealed changes in 1120 metabolites, with 31 co-expressed, mainly in energy and amino acid metabolism. Small extracellular vesicles (SEVs) concentrations and EGFR levels were significantly altered. Correlation analysis identified a relationship between these biomarkers, implying their potential significance as early events in the initiation and progression of lung cancer. These findings provide valuable insights and a rationale for lung cancer screening and mechanistic investigations, thereby contributing to a deeper understanding of the disease.

Lung carcinoma (LC) is the primary cause of millions of deaths worldwide. As LC is typically diagnosed at a later stage, its prevention and treatment are difficult. The pathological basis of both types of LC, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), is highly determined. The only treatments available for LC are surgical resection and chemotherapy, which require sophisticated new treatments. Biomarkers are promising treatment options, because they can be used for both diagnosis and treatment. Typical signaling molecules known as biomarkers identify abnormalities in cellular activity and serve as prognostic and diagnostic indicators. Biomarkers show great promise in clinical decision making, early and quick diagnosis, recurrence of illness, and tracking the effectiveness of cancer treatments. This review provides an overview of biomarkers, their benefits, and future directions for those new to the field of biomarker research in LC therapy.

Patients with hard-to-treat or rare cancers and those not responding to standard-of-care (SoC) treatment have unmet needs. Limited access to novel drugs is an increasing additional challenge. In 2003, the Danish government adopted a Health Act to ensure that treatment of patients with life-threatening disease could be reevaluated by independent experts. The Danish Health Authority (DHA) set up an Expert Advisory Panel to provide advice on possibilities for further treatment of patients, including treatment not approved nationally. A few years later, clinical units were established that could offer unestablished treatment to patients by referral from the Panel. The treatment was first reimbursed by the Government and later by regional authorities.

We present the structure, workflow, and impact of the Health Act for 21 years for patients with cancer. Annual reports from the DHA were the primary data source.

11 034 cases from 9603 cancer patients were evaluated by the Panel from 2003 to 2023, representing a median of 372 unique cases yearly. In 53%, the Panel advised on further treatment in Denmark, and of these, 56% were recommended nationally nonapproved treatment, 21% SoC treatment or workup, and 19% clinical trial participation. In 4.5% of cases, advice was given on treatment abroad. A significant decline in admissions to the Panel from a peak of 1167 patients in 2008 to 3-400 yearly from 2012 to 2017 followed the conversion of nonapproved treatments to SoC practice. A shift in drug reimbursement, independent of Panel advise, reduced the clinical impact and explained the further decline observed in admissions lately to only 51 patients in 2023.

This unique national scheme provided early access to treatment for patients with no further SoC options and facilitated the introduction of new cancer treatments, initiation of clinical trials, and establishment of trial units in the country. The scheme may be adapted to other countries with a public healthcare system. Results of the current report indicate that impact is dependent on delivering clinical units and reimbursement associated with the recommended treatment.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant efficacy in patients with brain metastases (BMs) from EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable, and clinical data addressing key questions across treatment stages remain insufficient, limiting the formulation of precise treatment strategies.

This retrospective study analyzed 302 EGFR-mutant NSCLC patients with BMs treated at Shandong Cancer Hospital (2014-2022). Patients were divided into three cohorts: cohort A (first-/second-generation EGFR-TKIs without third-generation use), cohort B (first-/second-generation followed by third-generation EGFR-TKIs), and cohort C (first-line third-generation EGFR-TKIs). Survival outcomes were evaluated using Kaplan-Meier and Cox regression analyses across three treatment stages. Propensity score matching (PSM) adjusted for baseline imbalances.

Third-generation EGFR-TKIs demonstrated superior progression-free survival (PFS) in first-line therapy compared to earlier-generation agents (median PFS1: 14.2 vs. 11.2 months; p = 0.0021), particularly for intracranial control (median iPFS1: 18.0 vs. 12.2 months; p = 0.0058). Patients with uncommon EGFR mutations had significantly shorter PFS on third-generation EGFR-TKIs than those with common mutations (4.4 vs. 12.9 months; p = 0.012). After resistance, combination therapy with immune checkpoint inhibitors (ICIs), antiangiogenics, and chemotherapy extended overall survival (OS) versus non-ICI regimens (median OS2: 17.3 vs. 10.4 months; p = 0.004).

Third-generation EGFR-TKIs are effective first-line options for BMs but show limited efficacy against uncommon mutations. Post-resistance regimens integrating ICIs, antiangiogenics, and chemotherapy may improve survival. Reassessment of genetic and PD-L1 status is critical for guiding sequential therapy.

Epidermal growth factor receptor (EGFR) mutations, especially in non-small cell lung cancer (NSCLC), present significant challenges to targeted therapies due to acquired resistance. This study reports the synthesis and evaluation of a series of 4-(2-substituted-6-(furan-2-yl)pyrimidin-4-yl)-substituted phenyl derivatives as potential anticancer agents. The compounds were screened using MTT and brine shrimp lethality assays, identifying R2, R10, and R12 as the most potent against NSCLC cell lines, particularly NCI-H522 and NCI-H1975. Compound R12 was most potent and selective against NCI-H522, with an IC50 value of 0.95 ± 0.02 µM as compared to standard afatinib (IC50 = 1.86 ± 0.22 µM). EGFR inhibition assays confirmed R12 effectiveness with IC50 values of 1.62 ± 0.15 µM, 0.49 ± 0.23 µM, and 0.98 ± 0.02 µM against EGFRWT, EGFRT790M, and EGFRL858R/T790M/C797S, respectively. The compound R12 led to the cell cycle arrest in the G2/M and S phase of NCI-H522 cells with an increase in apoptosis. Molecular docking studies showed R12 high binding affinity (ΔG = -10.2 kcal/mol for EGFRWT; Ki = 32.73 nM) and significant interactions with key amino acids in the active site. Molecular dynamics simulations demonstrated stable protein-ligand interactions with low RMSD (0.17-0.27 nm) and significant eigenvalue (1.706 × 10-4). Compound R12 also exhibited antioxidant properties against DPPH (IC50 = 12.11 ± 8.96 µM) and H2O2 (IC50 = 8.89 ± 1.72 µM). Furthermore, DFT analysis and ADMET predictions indicated that R12 possesses favorable physiochemical and pharmacokinetic properties, suggesting high bioavailability and minimal toxicity. These findings emphasize R12 as a promising lead for further preclinical investigation in overcoming EGFR mutations, including the challenging triple mutation.

Areca nut (AN) was classified as a carcinogen by the International Agency for Research on Cancer (IARC) of the WHO in 2003. AN has the same carcinogenic components as cigarettes, such as benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), but its effects on interactions with genetic factors related to lung cancer have rarely been investigated.  METHODS: Here, a propensity score-matched case‒control study was conducted in Hainan, which included 445 patients with lung cancer and 445 cancer-free controls. Then, the associations between single-nucleotide polymorphisms (SNPs) in the CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction effects with AN chewing and smoking on lung cancer were analyzed. In addition, we explored the associations among AN, cigarettes, and genes related to lung cancer using the Comparative Toxicogenomics Database (CTD).

The results indicate that the CHRNA3 rs938682 (A > G) GG genotype (OR = 0.669, 95% CI = 0.454 ~ 0.984, P = 0.042) can decrease the risk of lung cancer. The CHRNB4 rs7178270 (C > G) GG genotype (OR = 1.729, 95% CI = 1.168 ~ 2.571, P = 0.006) can increase the risk of lung cancer. The CHRNA5 rs17486278 CC genotype was associated with a high risk in males, smokers, and drinkers. The CHRNA3 rs938682 GG genotype was associated with a low risk in AN chewers. The CHRNB4 rs7178270 GG genotype was associated with high risk in drinkers and AN chewers. CHRNB4 rs7178270 and AN chewing have an interaction effect on lung cancer in Hainan.

This study is the first to elucidate the hidden impacts of AN on lung cancer and provides a key evidence regarding the interactive effects of AN and cigarettes with SNPs in nAChRs genes on lung cancer.

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the EGFR gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared with EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (odds ratio = 8.63, 95% confidence interval: 5.67-13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (odds ratio = 3.50, 95% confidence interval: 2.44-5.00) (p-heterogeneity = 3.66 × 10-3). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.

Lung cancer (LC) is one of the most common causes of cancer-related death worldwide. It has been demonstrated that the prognosis of current drug treatments is affected by a variety of factors, including late stage, tumor recurrence, inaccessibility to appropriate treatments, and, most importantly, chemotherapy resistance. Non-coding RNAs (ncRNAs) contribute to tumor development, with some acting as tumor suppressors and others as oncogenes. The phosphoinositide 3-kinase (PI3Ks)/AKT serine/threonine kinase pathway is one of the most important common targets of ncRNAs in cancer, which is widely applied to modulate the cell cycle and a variety of biological processes, including cell growth, mobility survival, metabolic activity, and protein production. Discovering the biology of ncRNA-PI3K/AKT signaling may lead to advances in cancer diagnosis and treatment. As a result, we investigated the expression and role of PI3K/AKT-related ncRNAs in clinical characteristics of lung cancer, as well as their functions as potential biomarkers in lung cancer diagnosis, prognosis, and treatment.

Non-small cell lung cancer (NSCLC) is a common cause of cancer-related deaths worldwide, and its incidence has been increasing in recent years. While targeted therapies like osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor, have brought about notable improvements in patient outcomes for advanced NSCLC, the challenge of acquired drug resistance persists. Here, we found that cellular mesenchymal-epithelial transition factor (c-Met) was highly expressed in osimertinib-resistant cells, and depletion of c-Met markedly inhibited the growth of osimertinib-resistant cells ex vivo and in vivo, suggesting that c-Met is a potential target to address osimertinib resistance. Through a screening process using a natural product compound library, we identified piperlongumine as a potent inhibitor to overcome osimertinib resistance. Furthermore, the combined treatment of piperlongumine and osimertinib exhibited robust antitumor effects in resistant cells, partially restoring their sensitivity to osimertinib. Additionally, we discovered that piperlongumine could enhance the interaction between E3 ligase RNF4 and Sp1, inhibit the phosphorylation of Sp1 at Thr739, facilitate the ubiquitination and degradation of Sp1, lead to c-Met destabilization, and trigger intrinsic apoptosis in resistant cells. In summary, our study sheds light on the potential of piperlongumine in overcoming osimertinib resistance, offering new strategies and perspectives for the clinical management of drug-resistant NSCLC.

The ADAURA study indicated that adjuvant TKI therapy improves survival in postoperative patients with EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC), especially in stage III disease. However, the effect of PORT for stage III (N2) NSCLC with different EGFR statuses remains unclear, which we aimed to investigate in the present study.

Between 2006 and 2019, consecutive patients with pN2 non-squamous cell NSCLC (Nsq-NSCLC) after complete resection and adjuvant chemotherapy or EGFR tyrosine kinase inhibitor (TKI) who had detection of EGFR status were retrospectively analyzed. PORT was administered using IMRT at 2 Gy per fraction with a total dose of 50 Gy over 5 weeks. Patients were categorized into 4 groups according to EGFR status and treatment: EGFR wild-type (EGFRwt) PORT group, EGFRwt non-PORT group, EGFRm PORT group, and EGFRm non-PORT group. Propensity score matching (PSM) was used to compensate for differences in baseline characteristics. The Kaplan-Meier method and log-rank test were used to evaluate disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS).

A total of 566 patients were enrolled: 90 in the EGFRwt PORT group, 154 in the EGFRwt non-PORT group, 111 in the EGFRm PORT group, and 211 in the EGFRm non-PORT group. After PSM, the median DFS in the EGFRwt PORT group versus the EGFRwt non-PORT group were 33.9 versus 17.2 months (HR 0.62, 95%CI 0.417-0.920, P = 0.017). In EGFRwt groups, PORT also improved LRFS (HR 0.58, 95%CI 0.34-0.99, P = 0.042) and DMFS (HR 0.649, 95%CI 0.43-0.98, P = 0.038). In EGFRm groups, PORT only improved LRFS (HR 0.50, 95%CI 0.30-0.85, P = 0.009), with no significant difference in DFS or DMFS between the PORT and non-PORT groups.

For patients with completely resected pN2 Nsq-NSCLC receiving adjuvant chemotherapy, PORT may improve DFS in EGFRwt patients but not in EGFRm patients. Randomized clinical trials are needed for validation.

This study seeks to identify research trends and hotspots concerning tyrosine kinase inhibitors (TKIs) for the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) through a comprehensive bibliometric analysis.

Publications on TKIs and EGFR-mutated NSCLC from 2006 to 2024 were analyzed using VOSviewer, CiteSpace, and R-bibliometrix to visualize collaboration, keyword co-occurrences, and research trends.

A total of 962 articles were analyzed, authored by 7,458 researchers from 5,401 institutions across 208 countries. Wu Yi-Long was identified as the most prolific author, contributing 30 publications. AstraZeneca emerged as the industrial leader with 103 articles, while the New England Journal of Medicine was recognized as the primary journal with the highest total link strength. Keyword co-occurrence analysis revealed significant research topics including "gefitinib", "chemotherapy", "open label", and "erlotinib." Moreover, keyword burst analysis indicated notable periods of increased research focus on topics such as "osimertinib" and "liquid biopsy", suggesting emerging trends and current hotspots in the treatment of EGFR-mutated NSCLC.

This analysis highlights research trends on TKIs for EGFR-mutated NSCLC, emphasizing the importance of targeted therapies like gefitinib and osimertinib for future research and clinical practice enhancement.

In recent years, hyperoside (quercetin 3-O-β-D-galactopyranoside) has garnered significant attention due to its diverse biological effects, which include vasoprotective, antioxidant, anti-inflammatory, and anti-tumor properties. Notably, hyperoside has shown remarkable potential in cancer therapy by targeting multiple mechanisms; it induces apoptosis, inhibits proliferation, blocks angiogenesis, and reduces the metastatic potential of cancer cells. Furthermore, hyperoside enhances the sensitivity of cancer cells to chemotherapy by modulating key signaling pathways. Beyond neoplastic diseases, hyperoside also presents promising therapeutic applications in managing non-cancerous conditions such as diabetes, Alzheimer's disease, and pulmonary fibrosis. This review comprehensively examines the molecular mechanisms underlying hyperoside's anti-cancer effects and highlights its role in the treatment of cancers, including lung and colorectal cancers. Additionally, it explores the latest research on hyperoside's potential in addressing non-neoplastic conditions, such as pulmonary fibrosis, diabetes, and Parkinson's disease. By summarizing current findings, this review underscores the unique therapeutic value of hyperoside and its potential as a multifunctional treatment in both neoplastic and non-neoplastic contexts.

Lung adenocarcinoma (LUAD) is one of the most common and lethal tumors. The identification of diagnostic and prognostic biomarkers is essential to improve patient prognosis and treatment outcomes.

The expression of minichromosome maintenance complex component 8 (MCM8) in 33 cancer types was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression. Tumor and normal tissues in LUAD were compared using TCGA data and validated against four datasets from the Gene Expression Omnibus. MCM8 expression was assessed by immunohistochemistry (IHC) using tissue microarrays. The diagnostic value of MCM8 was assessed by Receiver Operating Characteristic curve analysis, and its prognostic significance was determined by Kaplan-Meier analysis. The CIBERSORT method was used to examine immune infiltration. The association between MCM8 expression and m6A RNA methylation, glycolysis, and ferroptosis was assessed using the GEPIA online tool.

MCM8 is markedly overexpressed in many tumors including LUAD. MCM8 showed high accuracy for the diagnosis of LUAD, with an area under the curve of 0.849 in TCGA dataset. MCM8 overexpression in tumor tissues in LUAD was confirmed by IHC and shown to be associated with decreased overall survival and disease-specific survival. Analysis of immune cell infiltration showed that immune cell populations differed between high and low MCM8 expression groups. MCM8 expression correlated with that of genes associated with m6A RNA methylation, glycolysis, and ferroptosis.

MCM8 was identified as a promising diagnostic and prognostic marker in LUAD. The mechanism underlying the effect of MCM8 on cancer development and the immune response remains to be elucidated.

Non-small-cell lung cancer (NSCLC) is the most common lung cancer subtype, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the core drugs used for its treatment. However, the emergence of drug resistance poses a significant challenge to their clinical efficacy. As a significant role-player in cancer development and maintenance, histone modifications, DNA methylation and noncoding RNA (ncRNA) changes have been proven to play a crucial part in driving EGFR-TKI resistance, which provides promising potential therapeutic targets and biomarkers for overcoming drug resistance. This review delves into the complex epigenetic mechanisms that cause EGFR-TKI resistance and emphasizes the potential of combined epigenetic therapies, aiming to provide better-targeted treatment options for NSCLC patients with NSCLC and drive innovative strategies to overcome the challenges of drug resistance.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The identification of new biomarkers is crucial for enhancing early detection and treatment outcomes. This study explores the role of Canopy FGF Signaling Regulator 2 (CNPY2) in NSCLC progression and its potential as a diagnostic and prognostic biomarker.

CNPY2 expression was analyzed in 228 NSCLC tumor samples and adjacent normal tissues using quantitative RT-PCR and ELISA. Serum CNPY2 levels were also measured in 160 healthy controls and NSCLC patients. The relationship between CNPY2 expression and clinicopathological features, including epithelial-mesenchymal transition (EMT) markers, was assessed. Receiver operator curve analysis was used to evaluate the diagnostic potential of serum CNPY2, while Kaplan-Meier survival analysis assessed its prognostic significance.

CNPY2 levels were significantly elevated in NSCLC tissues compared to adjacent normal tissues. Higher CNPY2 expression was associated with larger tumor size, advanced T stage, and higher N stage. Furthermore, CNPY2 expression was positively correlated with Vimentin and N-cadherin, and negatively correlated with E-cadherin. Elevated serum CNPY2 levels in NSCLC patients demonstrated moderate diagnostic accuracy, with an area under the curve of 0.78. High CNPY2 expression was also linked to reduced overall survival (p = 0.001).

CNPY2 is markedly overexpressed in NSCLC and is associated with increased tumor aggressiveness and EMT. Serum CNPY2 shows promise as a non-invasive biomarker for NSCLC diagnosis, and elevated expression is correlated with a poorer prognosis. Thus, CNPY2 may serve as both a valuable biomarker and a potential therapeutic target in NSCLC.

Rhododendron anthopogon D.Don is an evergreen shrub used by Himalayan healers to treat many ailments most notably lung problems. However, the mechanism by which R. anthopogon essential oil fights lung cancer has not been well studied. Here, in the present study, we used network pharmacology in combination with chemical profiling, molecular docking, and in-vitro experimental studies to uncover the mechanism of R. anthopogon essential oil constituents against lung cancer. By employing network pharmacology-based analysis, a total of 266 potential target genes obtained for 12 active components of R. anthopogon interacted with 260 common targets and 17,731 disease targets associated with lung cancer were retrieved. Using protein-protein interaction network (PPI), search tool for the retrieval of interacting genes/proteins (STRING) and database for annotation, visualization, and integrated discovery (DAVID) databases, we predicted that the main signaling pathways involved in the association of lung cancer with R. anthopogon essential oil constituents are the cancer signaling pathway and vascular endothelial growth factor and its receptor (VEGFR) cancer signalling pathway. Using TIMER 2.0 analysis and University of Alabama Cancer Database (UALCAN) findings, the expression pattern of EGFR was investigated across all TCGA (The cancer genome atlas) datasets. The study revealed that EGFR expression was elevated in various cancers especially in lung adenocarcinoma. Molecular docking analysis revealed that linalool, α-bisabolol, and guaiol possessed strong binding affinity with TNF-α, MAPK3, and EGFR protein drug targets. Our results predicted that TNF-α, MAPK3, and EGFR may be potential molecular targets of R. anthopogon essential oil constituents for the treatment of lung cancer. Furthermore, our study verified that R. anthopogon essential oil constituents inhibit proliferation, and induces apoptosis in lung cancer cell lines. Therefore, the present study highlights anti-lung cancer activity of the constituents of R. anthopogon essential oil and its potential involvement in comprehending therapeutic mechanism that may be applied in the lung cancer therapy.

Lung cancer remains a major global health challenge and one of the leading causes of cancer-related deaths worldwide. Despite significant advancements in treatment, challenges such as drug resistance, side effects, metastasis and recurrence continue to impact patient outcomes and quality of life. In response, there is growing interest in complementary and integrative approaches to cancer care. Traditional Chinese medicine (TCM), with its long history, abundant clinical experience, holistic perspective and individualized approach, has garnered increasing attention for its role in lung cancer prevention and management. This review provides a comprehensive overview of the advances in TCM for lung cancer treatment, covering its theoretical foundation, treatment principles, clinical experiences and evidence supporting its efficacy. We also provide a systematic summary of the preclinical mechanisms, through which TCM impacts lung cancer, including the induction of cell death, reversal of drug resistance, inhibition of metastasis and modulation of immune responses. Additionally, future prospects for TCM in lung cancer treatment are discussed, offering insights into its expanded application and integration with modern medicine to address this challenging disease.

While clinical trials have demonstrated enduring responses to amivantamab among advanced non-small cell lung cancer (NSCLC) patients bearing EGFR exon 20 insertion mutations, the associated toxicity profile in real-world scenarios remains elusive.

This pharmacovigilance study analyzed data from the FDA Adverse Event Reporting System (FAERS) to investigate adverse events associated with amivantamab over the period from September 2021 to December 2023. A comprehensive disproportionality analysis was performed, employing the reporting odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and the Bayesian confidence propagation neural network to calculate information components (ICs), to identify statistically significant adverse events.

A significant proportion of adverse events (AEs) was attributable to injury, poisoning, and procedural complications, cutaneous disorders, respiratory ailments, infections, as well as vascular and lymphatic system disturbances. There were noteworthy incidences of AEs including infusion-related reactions, rash, dyspnea, pneumonitis, paronychia, pulmonary embolism, thrombocytopenia, nausea, acneiform dermatitis, deep vein thrombosis, febrile neutropenia, peripheral edema, hypokalemia, and neutropenia. Furthermore, the majority of AEs occurred within the first month following the initiation of amivantamab treatment, accounting for 51.74% of cases.

The reversibility of amivantamab-related toxicities suggests its promising utility in patients with EGFR exon 20 insertion mutations NSCLC.

Lung cancer, a leading cause of cancer-related deaths worldwide, is primarily linked to smoking, tobacco use, air pollution, and exposure to hazardous chemicals. Genetic alterations, particularly in oncogenes like RAS, EGFR, MYC, BRAF, HER, and P13K, can lead to metabolic changes in cancer cells. These cells often rely on glycolysis for energy production, even in the presence of oxygen, a phenomenon known as aerobic glycolysis. This metabolic shift, along with other alterations, contributes to cancer cell growth and survival. To develop effective therapies, it's crucial to understand the genetic and metabolic changes that drive lung cancer. This review aims to identify specific genes associated with these metabolic alterations and screen phytochemicals for their potential to target these genes. By targeting both genetic and metabolic pathways, we hope to develop innovative therapeutic approaches to combat lung cancer.

It is important to systematically identify tumor suppressor genes (TSGs) to improve our understanding of tumorigenesis and develop strategies for early diagnosis and mitigating disease progression. In the present study, we used an in vivo genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) screen and identified FPS/FES-related (FER) as a TSG. Single-cell RNA sequencing (scRNA-seq) revealed that normal cells with low FER expression exhibited elevated malignant transformation potential and stemness properties. FER knockout promoted the tumorigenic transformation, characterized by high colony-forming efficiency and suspension growth ability, acquired tumorigenicity in vivo, increased metabolic activity, dedifferentiation properties, and immune evasion. Moreover, analysis revealed that low FER expression tumors share molecular phenotypes with FER knockout cells, suggesting the consistent role of FER in tumor initiation and progression. Taken together, our findings not only provide insights into the essential role of FER as a tumor suppressor in tumor initiation and progression but also highlight its potential as a target for future clinical diagnosis. © 2024 The Pathological Society of Great Britain and Ireland.

Cancer immunotherapy holds significant promise for improving cancer treatment efficacy; however, the low response rate remains a considerable challenge. To overcome this limitation, advanced catalytic materials offer potential in augmenting catalytic immunotherapy by modulating the immunosuppressive tumor microenvironment (TME) through precise biochemical reactions. Achieving optimal targeting precision and therapeutic efficacy necessitates a thorough understanding of the properties and underlying mechanisms of tumor-targeted catalytic materials. This review provides a comprehensive and systematic overview of recent advancements in tumor-targeted catalytic materials and their critical role in enhancing catalytic immunotherapy. It highlights the types of catalytic reactions, the construction strategies of catalytic materials, and their fundamental mechanisms for tumor targeting, including passive, bioactive, stimuli-responsive, and biomimetic targeting approaches. Furthermore, this review outlines various tumor-specific targeting strategies, encompassing tumor tissue, tumor cell, exogenous stimuli-responsive, TME-responsive, and cellular TME targeting strategies. Finally, the discussion addresses the challenges and future perspectives for transitioning catalytic materials into clinical applications, offering insights that pave the way for next-generation cancer therapies and provide substantial benefits to patients in clinical settings.

Non-small cell lung cancer (NSCLC) has a strikingly high incidence rate globally. Although immunotherapy brings a great breakthrough in its clinical treatment of NSCLC, significant challenges still need to be overcome. The development of novel multi-functional nanomedicines in the realm of tumor immunotherapy offers promising opportunities for NSCLC patients, as nanomedicines exhibit significant advantages, including specific targeting of tumor cells, improved drug bioavailability, reduced systemic toxicity, and overcoming of immune resistance. In this review, the core features and current clinical status of strategies for NSCLC immunotherapy including immune checkpoint blockade, antibody-drug conjugates, cell engagers, adoptive cells, and cancer vaccines, are surveyed. Particular emphasis is placed on the recent development of nanomedicines that boost these strategies. Nanomedicine can provide novel perspectives for NSCLC immunotherapy.

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in the treatment of EGFR mutation-positive advanced non-small cell lung cancer. Osimertinib-induced cutaneous vasculitis is a rare skin adverse reaction. We present a case study of a 49-year-old female who developed palpable purpura on her lower extremities on the 11th day of osimertinib treatment. Systemic involvement was not observed in the test results. The multidisciplinary team considered the clinical presentation of purpura as a potential case of cutaneous vasculitis. Osimertinib was immediately discontinued, and intravenous methylprednisolone along with oral cetirizine treatment was initiated. After 8 days since discontinuation of osimertinib, the patient's skin purpura completely subsided. Subsequently, she was switched to almonertinib for treatment. We also conducted a literature review cutaneous vasculitis induced by osimertinib and other EGFR-TKIs. We hope to provide some safety alert information for clinical practice and recommend enhanced monitoring during the medication process.

This study aimed to identify the genes associated with the development of lung adenocarcinoma (LUAD) and potential therapeutic targets.

Differentially expressed genes (DEGs) were identified by self-transcriptome sequencing of tumor tissues and paracancerous tissues resected during surgery and combined with The Cancer Genome Atlas (TCGA) data to screen for the genes associated with LUAD prognosis. The expression was validated at mRNA and protein levels, and the gene knockdown was used to examine the impact and underlying mechanisms on lung cancer cells.

A total of 227 DEGs were identified by transcriptome sequencing, and the 20 DEGs with the most significant differences were used for co-analysis with TCGA data. The findings suggested that KRT16 and ANXA10 might have an important role in the development of LUAD after validating the mRNA and protein expression levels at the cellular level. The knockdown of KRT16 and ANXA10 inhibited the proliferation of lung cancer cells, and the cell cycle was blocked in the G1 phase. The expression of the G1/S-phase cell cycle checkpoint-related proteins cyclin D1 and cyclin E was inhibited by KRT16 and ANXA10 knockdown, respectively. The tumor formation ability decreased after KRT16 or ANXA10 knockdown in vivo.

KRT16 and ANXA10 are potential genes regulating the development of LUAD. Also, they may be potential targets for the targeted therapy of LUAD by inhibiting the proliferation of lung cancer cells and blocking the cell cycle by affecting key protein expression levels at cell cycle checkpoints.