While biomarker-guided treatments and NGS-based approaches are refining precision medicine, they are not universally applicable. The gap between the genomic characterization of tumors and their functional behavior is becoming increasingly evident. There is an escalating demand for functional assays that can customize cancer treatments for individual patients and bridge this gap. We have developed OncoFlow, an integrated microfluidic platform that automates viability assays. This platform customizes treatment options by assessing the functional responses of a patient's tumor cells to a specific drug panel. This study specifically addressed non-small cell lung adenocarcinoma (NSCLC) in patients presenting pleural effusion. We used the NCI-H2228 adenocarcinoma cell line, which harbors the EML4-ALK fusion oncogene, to develop and fine-tune the viability assay. Cells cultivated in microfluidic chambers were treated with various concentrations of the tyrosine kinase inhibitors alectinib and crizotinib, and the cytotoxic effects were measured. The results were consistent with those from conventional cell culture methods, thereby validating the assay's reliability. Next, pleural effusion samples from six NSCLC patients, four of them harboring the EML4-ALK rearrangement were tested with alectinib and crizotinib using the OncoFlow system. Monitoring and analysis of cell viability showed varied sensitivities to crizotinib, while all samples exhibited resistance to alectinib. These findings underscore OncoFlow's potential to enhance physician decision-making and customize treatment plans, ultimately improving patient outcomes.

Over the past few years, immune checkpoint inhibitors resulted in magnificent and durable successes in treating cancer; however, only a minority of patients respond favorably to the treatment due to a broad-spectrum of tumor-intrinsic and tumor-extrinsic factors. With the recent insights gained into the mechanisms of resistance, combination treatment strategies to overcome the resistance and enhance the therapeutic potential of immune checkpoint inhibitors are emerging and showing promising results in both pre-clinical and clinical settings. This has been derived through multiple interconnected mechanisms such as enhancing tumor immunogenicity, improving neoantigen processing and presentation in addition to augmenting T cell infiltration and cytotoxic potentials. In the clinical settings, several avenues of combination treatments involving immune checkpoint inhibitors were associated with considerable improvement in the therapeutic outcome in terms of patient's survival and tumor growth control. This, in turn, increased the spectrum of cancer patients benefiting from the unprecedented and durable effects of immune checkpoint inhibitors leading to their adoption as a first-line treatment for certain cancers. Moreover, the significance of precision medicine in cancer immunotherapy and the unmet demand to develop more personalized predictive biomarkers and treatment strategies are also highlighted in this review.

Characteristics of tumors and patients can be used as predictive biomarkers to guide treatment choice. Although many potential biomarkers are evaluated each year, only few will eventually be used since evidence is usually based on small studies leading to inconclusive results. Such data are often analyzed with Cox proportional hazards regression using a multiplicative interaction term between biomarker and treatment, with insufficient power and possibly biased results. Instead of analyzing patients who do (cases) and do not experience (non-cases) the survival event of interest, case-only analysis with logistic regression has been proposed, however with unknown small sample properties. We evaluated the performance of case-only analysis with bias-eliminating Firth correction and confidence intervals obtained with a profile likelihood method in a simulation study tailored to breast cancer. Our results show that this approach is generally inferior to the full cohort analysis but has acceptable properties when the marker is protective or null among patients treated with the standard treatment, the event rate is low (e.g., a rare event and a protective marker) and treatment assignment is independent of the marker level (e.g., in randomized studies). In such situations, the case-only design offers substantial cost savings. However, the model is sensitive to these assumptions.

Breast magnetic resonance imaging (MRI) is considered the most effective method for detecting breast cancer due to its high sensitivity. Yet multiple factors limit its widespread use, including high direct and indirect costs, a prolonged acquisition time with consequent patient discomfort, and a lack of trained radiologists. During the last decade, new strategies have been followed to increase the availability of breast MRI, including the omission of non-essential sequences to generate abbreviated MRI protocols (AB-MRIs) aimed at reducing the acquisition time with the potential of improving the patient's experience and accommodating a higher number of MRI examinations per day. An alternative method is ultrafast MRI (UF-MRI), a novel technique that gathers kinetic data within the first minute after contrast injection, offering high temporal resolution. This enables the analysis of early contrast wash-in curves, showing promising outcomes. In this study, we reviewed the role of UF-MRI in breast imaging and detailed how the integration of this new approach with radiomics and mathematical models might further improve diagnostic accuracy and even have a prognostic role, a fundamental characteristic in the modern scenarios of personalized medicine. In addition, possible clinical applications and advantages of UF-MRI will be discussed.

Patients with serious conditions face complex, long-lasting patient journeys involving multiple healthcare providers. Research shows that these journeys are frequently perceived as fragmented, with significant challenges in communication and information flow. However, there is limited knowledge about the organisational and informational aspects linked to good and poor experiences. This study investigated critical factors in cancer journeys, focusing on communication and the informational and organisational elements shaping patient experiences.

The critical incident technique was used to identify positive and negative factors in cancer patient journeys. People with cancer and their next-of-kin were recruited through Norway's national cancer organisation. Patient episodes were collected from 41 participants via digital workshops combined with questionnaires and supplemented by in-depth interviews. Critical incidents were extracted using specific analytical criteria.

A total of 187 critical incidents were identified, including 81 positive and 106 negative. Content analysis revealed 12 categories of incidents. Positive incidents were linked to effective communication, timely information, and well-coordinated care, particularly through cancer pathways. Negative incidents often involved communication delays, insensitive information delivery, and poor coordination among healthcare providers. Notably, around 40% of the negative incidents stemmed from fragmented health services or a lack of progress, often forcing patients to act as messengers.

By examining critical experiences, this study highlights key areas for improving cancer care. Timely information and clinical empathy when delivering sensitive diagnoses are essential. Healthcare providers must coordinate services more effectively to prevent patients from intervening to ensure care progress.

Patients' stories formed the core data. The public contributed to recruitment, while patient feedback informed the workshop design.

Immunotherapy has become one of the innovative treatments in malignancy as it activates the immune system to find and eliminate malignant cells. The tumor immunology interface has become increasingly intricate, making the identification of new immune targets and signalling pathways on which to base improved therapeutic strategies an ongoing process. This review, we goal to clarify the contacts between cancer and immune system with a focus on immune surveillance as well as immune evasion mechanisms. Comprehensive immunotherapeutic therapies are overviewed with ICI (CTLA-4, PD-1, PD-L1), CAR-T cell therapy, and cancer vaccines whereas, advanced therapies targeting new immune checkpoints are also elucidated including TIM-3, LAG-3, and TIGIT. The JAK/STAT, MAPK and PI3K-AKT-mTOR pathways are reviewed with regards to cancer progression and immunotherapeutic resistance. The dysregulation of these pathways gives hope for the identification of fresh targets for therapy. Genomics, proteomics, immunopeptidomics, single cell mass spectrometry, CRISPR-based functional genomics and bioinformatics are described as essential for immune target identification and for mapping of cancer relevant signaling pathways. This review also considers some emerging issues in the subject area like the tumor heterogeneity, immune-related adverse events (irAEs), and personalized treatment. These barriers are described to facilitate the understanding of ways to overcome them and increase the efficacy of immunotherapies through combination therapies. This means that by developing new knowledge of immunological targets and pathways, immunoprecision medicine for cancer could greatly enhance outcomes.

Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to understand the genomic causes behind tumorigenesis, leading to more personalized approaches to diagnosis and treatment. Aberration of tumor suppressors, which undergo two-hit and loss-of-function mutations, and oncogenes, activated forms of proto-oncogenes that experience one-hit and gain-of-function mutations, are responsible for the dysregulation of key signaling pathways that regulate cell division, such as p53, Rb, Ras/Raf/ERK/MAPK, PI3K/AKT, and Wnt/β-catenin. Modern breakthroughs in genomics research, like next-generation sequencing, have provided efficient strategies for mapping unique genomic changes that contribute to tumor heterogeneity. Novel therapeutic approaches have enabled personalized medicine, helping address genetic variability in tumor suppressors and oncogenes. This comprehensive review examines the molecular mechanisms behind tumor-suppressor genes and oncogenes, the key signaling pathways they regulate, epigenetic modifications, tumor heterogeneity, and the drug resistance mechanisms that drive carcinogenesis. Moreover, the review explores the clinical application of sequencing techniques, multiomics, diagnostic procedures, pharmacogenomics, and personalized treatment and prevention options, discussing future directions for emerging technologies.

This paper highlights the innovative approach and findings of the recently published study by Xu et al, which underscores the integration of radiomics and clinicoradiological factors to enhance the preoperative prediction of microvascular invasion in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). The study's use of contrast-enhanced computed tomography radiomics to construct predictive models offers a significant advancement in the surgical planning and management of HBV-HCC, potentially transforming patient outcomes through more personalized treatment strategies. This editorial commends the study's contribution to precision medicine and discusses its implications for future research and clinical practice.

Burn-induced sepsis is a critical clinical challenge marked by systemic inflammation, immune dysregulation, and high mortality. Macrophage-driven inflammatory pathways are central to sepsis pathogenesis, while immune cell metabolic reprogramming plays a key role in both sepsis and cancer progression.

Bioinformatics analyses using GEO, TCGA, and GTEx datasets identified MLIP-modulated genes linked to immune responses and prognosis. In vitro, LPS-stimulated HUVEC cells were used to study MLIP's effects on inflammation and macrophage function through cell viability, ROS levels, cytokine expression, qRT-PCR, and immunofluorescence assays.

MLIP-modulated genes were associated with immune-related metabolic pathways in both sepsis and cancer. Epigenetic analysis showed MLIP expression is regulated by promoter methylation and chromatin accessibility. Prognostic analyses revealed MLIP's impact on survival outcomes across cancer types. In vitro, MLIP reduced inflammation, oxidative stress, and macrophage hyperactivation.

MLIP regulates immune-metabolic dynamics in burn-induced sepsis, influencing macrophage activity and oxidative stress. Its role in metabolic reprogramming suggests MLIP as a potential therapeutic target linking immune modulation and cancer progression. Further research on MLIP's role in immune evasion and tumor metabolism may inform novel therapeutic strategies.

E3 ubiquitin ligases, crucial enzymes in the ubiquitination pathway, significantly influence the development of malignant tumors, including gastric cancer (GC), by regulating the stability of oncogenic and tumor-suppressive proteins. This study employed bioinformatics analysis of public databases alongside various experimental techniques-tissue arrays, real-time reverse-transcription polymerase chain reaction, western blot, immunofluorescence, and coimmunoprecipitation-to identify and explore the role of HECW1, a pivotal NEDD4 family E3 ubiquitin ligase, in GC progression. The results demonstrated that HECW1 is markedly overexpressed in GC tissues relative to normal gastric tissues, and its elevated expression correlates with poor prognosis in GC patients. In vitro experiments revealed that HECW1 overexpression significantly enhances the metastatic capabilities of GC cells. Mechanistically, HECW1 interacts with HIPK2 to facilitate its ubiquitination and degradation, thereby activating AKT and promoting the expression of downstream epithelial mesenchymal transition-related genes. In vivo experiments confirmed HECW1's role in promoting GC cell metastasis, highlighting the HECW1-HIPK2-AKT signaling axis as critical in GC metastasis. These findings not only elucidate a novel metastasis mechanism of GC but also suggest potential molecular targets for developing new therapeutic strategies against GC.

Despite recent advances in cancer treatment, there is still a need for novel compounds with antineoplastic activity. Among 11 biphenyl-based organogold(III) N-heterocyclic carbene (NHC) (BGC) complexes of general formula [(C^C)Au(NHC-pyr)X], where (C^C) = 4,4'-ditertbutylbiphenyl, X = Cl or phenylacetylide, and (NHC-pyr) is a pyridyl-substituted NHC ligand, the complex BGC4 bearing a 4-CF3-pyridyl substituent and a chloride ligand showed promising antineoplastic activity on the triple negative breast cancer cell line. BGC4 was able to induce cell apoptosis but had no effect on the cell cycle. In vivo, BGC4 reduced the tumor growth rate by increasing the necrosis area and decreasing the mitotic activity. Repeated injections of BGC4 did not induce common side effects. The present investigation shows that BGC4 is a promising antineoplastic candidate. Its potential as a future chemotherapy for the treatment of cancer will be strengthened by evaluating its efficacy in combined treatment with current chemotherapy.

Cancer, a leading cause of global mortality, remains a significant challenge to increasing life expectancy worldwide. Forkhead Box R2 (FOXR2), identified as an oncogene within the FOX gene family, plays a crucial role in developing various endoderm-derived organs. Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases. Dysregulation of FOXR2 has been linked to numerous malignant tumors, spanning the brain, nervous system, thyroid, osteosarcoma, Hodgkin lymphoma, colorectal, liver, pancreatic, lung, breast, ovarian, prostate, female genital tract, endometrial, and uterine cancers. Despite extensive research on FOXR2 dysregulation, its practical applications remain underexplored. This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis, prognosis, and treatment.

Cardiogenic shock (CS) is a complex, multisystem disorder precipitated by hypoperfusion from cardiac dysfunction. Our current approach to defining and treating CS encompasses all patients under 1 umbrella regardless of phenotype. This has created challenges for clinical trials and patient care owing to the heterogeneity of the patient population with CS. The Society of Coronary Angiography and Interventions shock classification has created a universal language for CS that has been rapidly adopted by researchers and clinicians. Its latest iteration established the 3-axis model incorporating shock severity, risk modifiers, and phenotypes. Phenotypes of CS have unique hemodynamic profiles that require nuanced adjustment approaches. In this study, we discuss representative cases including acute myocardial infarction, acute-on-chronic heart failure, fulminant myocarditis, and right ventricular failure. For each phenotype, specific hemodynamic parameters may help confirm appropriate diagnosis and direct to therapeutic targets signaling stability and recovery. The underlying pathophysiology of each phenotype can also help predict the extent of stabilization with pharmacologic interventions or the need to escalate to mechanical circulatory support. In conclusion, this tailored approach to CS, rather than a 1-size-fits-all approach, could help improve outcomes.

Integrins are transmembrane receptors that play a crucial role in cell adhesion and signaling by connecting the extracellular environment to the intracellular cytoskeleton. After binding with specific ligands in the extracellular matrix (ECM), integrins undergo conformational changes that transmit signals across the cell membrane. The integrin-mediated bidirectional signaling triggers various cellular responses, such as changes in cell shape, migration and proliferation. Irregular integrin expression and activity are closely linked to tumor initiation, angiogenesis, cell motility, invasion, and metastasis. Thus, understanding the intricate regulatory mechanism is essential for slowing cancer progression and preventing carcinogenesis. Among the four classes of integrins, the arginine-glycine-aspartic acid (RGD)-binding integrins stand out as the most crucial integrin receptor subfamily in cancer and its metastasis. Dysregulation of almost all RGD-binding integrins promotes ECM degradation in ovarian cancer, resulting in ovarian carcinoma progression and resistance to therapy. Preclinical studies have demonstrated that targeting these integrins with therapeutic antibodies and ligands, such as RGD-containing peptides and their derivatives, can enhance the precision of these therapeutic agents in treating ovarian cancer. Therefore, the development of novel therapeutic agents is essential for treating ovarian cancer. This review mainly discusses genes and their importance across different ovarian cancer subtypes, the involvement of RGD motif-containing ECM proteins in integrin-mediated signaling in ovarian carcinoma, ongoing, completed, partially completed, and unsuccessful clinical trials of therapeutic agents, as well as existing limitations and challenges, advancements made so far, potential strategies, and directions for future research in the field. Insight Box Integrin-mediated signaling regulates cell migration, proliferation and differentiation. Dysregulated integrin expression and activity promote tumor growth and dissemination. Thus, a proper understanding of this complex regulatory mechanism is essential to delay cancer progression and prevent carcinogenesis. Notably, integrins binding to RGD motifs play an important role in tumor initiation, evolution, and metastasis. Preclinical studies have demonstrated that therapeutic agents, such as antibodies and small molecules with RGD motifs, target RGD-binding integrins and disrupt their interactions with the ECM, thereby inhibiting ovarian cancer proliferation and migration. Altogether, this review highlights the potential of RGD-binding integrins in providing new insights into the progression and metastasis of ovarian cancer and how these integrins have been utilized to develop effective treatment plans.

Cancer is a complex disease driven by mutations in the genes that play critical roles in cellular processes. The identification of cancer driver genes is crucial for understanding tumorigenesis, developing targeted therapies and identifying rational drug targets. Experimental identification and validation of cancer driver genes are time-consuming and costly. Studies have demonstrated that interactions among genes are associated with similar phenotypes. Therefore, identifying cancer driver genes using molecular network-based approaches is necessary. Molecular network-based random walk-based approaches, which integrate mutation data with protein-protein interaction networks, have been widely employed in predicting cancer driver genes and demonstrated robust predictive potential. However, recent advancements in deep learning, particularly graph-based models, have provided novel opportunities for enhancing the prediction of cancer driver genes. This review aimed to comprehensively explore how machine learning methodologies, particularly network propagation, graph neural networks, autoencoders, graph embeddings, and attention mechanisms, improve the scalability and interpretability of molecular network-based cancer gene prediction.

The incidence of cancer continues to increase worldwide, resulting in significant physical, emotional, and financial challenges for individuals, families, communities, and healthcare systems. Cancer is projected to be responsible for approximately 10 million deaths in 2020, accounting for one in six deaths globally. Prostate, colon, lung, and breast cancers are the most common types of cancer. In India, it is estimated that there will be around 2.7 million cancer patients by 2020. Personalized medicine has the potential to offer an alternative approach to cancer treatment. Precision medicine, often known as personalized medicine, is a new cancer treatment technique that focuses on tailoring medication to each patient's specific genetic, biochemical, and lifestyle factors. The goal is to optimize tumor response while minimizing therapy side effects, resulting in improved patient care and quality of life. Personalized medicine allows for the creation of focused medicines that address specific gene mutations by leveraging knowledge about a patient's cancer, including its genetic makeup. Ongoing research seeks to detect gene modifications in diverse cancer types, produce novel diagnostic tools, and develop treatments that particularly target these genetic changes. In recent years, personalized medicine has achieved major advances in the treatment of solid tumors, with the promise to improve treatment precision, reduce side effects, as well as enhance outcomes for patients in cancer therapy. This review aims to objectively evaluate the transformation of cancer treatment, emphasizing the shift towards a more precise methodology.

Lung cancer is among the most common instances of cancer subtypes and is associated with high mortality rates. Due to the availability of fewer therapies and delayed clinical investigations, the number of cancer incidences is rising dramatically. This is possibly an effect of immune modulations and chemotherapeutic drugs that raises cancer resistance. Among the list, IL-6 and IL-17 are host-derived paradoxical effectors that attune immune responses in malignant lung cells. Their excessive release in the cytokine milieu stabilizes immunosuppressive phenotypes, resulting in cellular perturbations. During tumor development, the significance of these molecules is reflected in their potential to regulate oncogenesis by initiating a myriad of signaling events that influence tumor growth and the metastatic ability of benign cancer cells. Moreover, their transactivation contributes to antiapoptotic mechanisms and favors cancer cell survival via constitutive expression of immunoregulatory molecules. Co-evolution and gene duplication events could be the major drivers behind cytokine evolution, which have prompted generic changes and, hence, the additive effect. The evolutionary model and statistical analysis provide evidence about the cytokines ancestral relationships and site-specific conservation, which is more convincing as both cytokines share cysteine-knot-like structures important in maintaining structural integrity. Funneling through the findings could help find residues that serve a catalytic role in immune functioning. Designing peptides or subunit vaccine formulations against those conserved residues could aid in combating lung cancer pathogenesis.

Malignant tumors remain one of the most significant global health challenges and contribute to high mortality rates across various cancer types. The complex nature of these tumors requires multifaceted diagnostic and therapeutic approaches. This review explores current advancements in diagnostic methods, including molecular imaging, biomarkers, and liquid biopsies. It also delves into the evolution of therapeutic strategies, including surgery, chemotherapy, radiation therapy, and novel targeted therapies such as immunotherapy and gene therapy. Although significant progress has been made in the understanding of cancer biology, the future of oncology lies in the integration of precision medicine, improved diagnostic tools, and personalized therapeutic approaches that address tumor heterogeneity. This review aims to provide a comprehensive overview of the current state of cancer diagnostics and treatments while highlighting emerging trends and challenges that lie ahead.

This review explores the integration of artificial intelligence (AI) in interventional radiotherapy (IRT), emphasizing its potential to streamline workflows and enhance patient care. Through a systematic analysis of 78 relevant papers spanning from 2002 to 2024, we identified significant advancements in contouring, treatment planning, outcome prediction, and quality assurance. AI-driven approaches offer promise in reducing procedural times, personalizing treatments, and improving treatment outcomes for oncological patients. However, challenges such as clinical validation and quality assurance protocols persist. Nonetheless, AI presents a transformative opportunity to optimize IRT and meet evolving patient needs.

Comprehensive genomic profiling (CGP) identifies genetic alterations and patterns that are crucial for therapy selection and precise treatment development. In Colombia, limited access to CGP tests underscores the necessity of documenting the prevalence of treatable genetic alterations. This study aimed to describe the somatic genetic profile of specific cancer types in Colombian patients and assess its impact on treatment selection.

A retrospective cohort study was conducted at Clínica Colsanitas S.A. from March 2023 to June 2024. Sequencing was performed on the NextSeq2000 platform with the TruSight Oncology 500 (TSO500) assay, which simultaneously evaluates 523 genes for DNA analysis and 55 for RNA; additionally, analyses were performed with the SOPHiA DDM software. The tumor mutational burden (TMB), microsatellite instability (MSI), and programmed cell death ligand 1 (PDL1) were assessed.

Among 111 patients, 103 were evaluated, with gastrointestinal (27.93%), respiratory (13.51%), and central nervous system cancers (10.81%) being the most prevalent. TP53 (37%), KMT2C (28%), and KRAS (21%) were frequent mutations. Actionable findings were detected in 76.7% of cases, notably in digestive (20 patients) and lung cancers (8 patients). MSI was stable at 82.52% and high at 2.91%, whilst TMB was predominantly low (91.26%).

The test has facilitated access to targeted therapies, improving clinical outcomes in Colombian patients. This profiling test is expected to increase opportunities for personalized medicine in Colombia.

Biological barriers remain a major obstacle for the development of innovative therapeutics. Depending on a disease's pathophysiology, the involved tissues, cell populations, and cellular components, drugs often have to overcome several biological barriers to reach their target cells and become effective in a specific cellular compartment. Human biological barriers are incredibly diverse and include multiple layers of protection and obstruction. Importantly, biological barriers are not only found at the organ/tissue level, but also include cellular structures such as the outer plasma membrane, the endolysosomal machinery, and the nuclear envelope. Nowadays, clinicians have access to a broad arsenal of therapeutics ranging from chemically synthesized small molecules, biologicals including recombinant proteins (such as monoclonal antibodies and hormones), nucleic-acid-based therapeutics, and antibody-drug conjugates (ADCs), to modern viral-vector-mediated gene therapy. In the past decade, the therapeutic landscape has been changing rapidly, giving rise to a multitude of innovative therapy approaches. In 2018, the FDA approval of patisiran paved the way for small interfering RNAs (siRNAs) to become a novel class of nucleic-acid-based therapeutics, which-upon effective drug delivery to their target cells-allow to elegantly regulate the post-transcriptional gene expression. The recent approvals of valoctocogene roxaparvovec and etranacogene dezaparvovec for the treatment of hemophilia A and B, respectively, mark the breakthrough of viral-vector-based gene therapy as a new tool to cure disease. A multitude of highly innovative medicines and drug delivery methods including mRNA-based cancer vaccines and exosome-targeted therapy is on the verge of entering the market and changing the treatment landscape for a broad range of conditions. In this review, we provide insights into three different disease entities, which are clinically, scientifically, and socioeconomically impactful and have given rise to many technological advancements: acquired immunodeficiency syndrome (AIDS) as a predominant infectious disease, pancreatic carcinoma as one of the most lethal solid cancers, and hemophilia A/B as a hereditary genetic disorder. Our primary objective is to highlight the overarching principles of biological barriers that can be identified across different disease areas. Our second goal is to showcase which therapeutic approaches designed to cross disease-specific biological barriers have been promising in effectively treating disease. In this context, we will exemplify how the right selection of the drug category and delivery vehicle, mode of administration, and therapeutic target(s) can help overcome various biological barriers to prevent, treat, and cure disease.

In exposure-response analyses of oral targeted anticancer agents, longitudinal plasma trough concentrations are often aggregated into a single value even though plasma trough concentrations can vary over time due to dose adaptations, for example. The aim of this study was to compare joint models to conventional exposure-response analyses methods with the application of alectinib as proof-of-concept.

Joint models combine longitudinal pharmacokinetic data and progression-free survival data to infer the dependency and association between the two datatypes. The results from the best joint model and the standard and time-dependent cox proportional hazards models were compared. To normalize the data, alectinib trough concentrations were normalized using a sigmoidal transformation to transformed trough concentrations (TTC) before entering the models.

No statistically significant exposure-response relationship was observed in the different Cox models. In contrast, the joint model with the current value of TTC in combination with the average TTC over time did show an exposure-response relationship for alectinib. A one unit increase in the average TTC corresponded to an 11% reduction in progression (HR, 0.891; 95% confidence interval, 0.805-0.988).

Joint models are able to give insights in the association structure between plasma trough concentrations and survival outcomes that would otherwise not be possible using Cox models. Therefore, joint models should be used more often in exposure-response analyses of oral targeted anticancer agents.

Varied expression of drug-metabolizing enzymes (DME) genes dictates the intensity and duration of drug response in cancer treatment. This study aimed to investigate the transcriptional profile of DMEs in tumor microenvironment (TME) at single-cell level and their impact on individual responses to anticancer therapy.

Over 1.3 million cells from 481 normal/tumor samples across 9 solid cancer types were integrated to profile changes in the expression of DME genes. A ridge regression model based on the PRISM database was constructed to predict the influence of DME gene expression on drug sensitivity.

Distinct expression patterns of DME genes were revealed at single-cell resolution across different cancer types. Several DME genes were highly enriched in epithelial cells (e.g. GPX2, TST and CYP3A5 ) or different TME components (e.g. CYP4F3 in monocytes). Particularly, GPX2 and TST were differentially expressed in epithelial cells from tumor samples compared to those from normal samples. Utilizing the PRISM database, we found that elevated expression of GPX2, CYP3A5 and reduced expression of TST was linked to enhanced sensitivity of particular chemo-drugs (e.g. gemcitabine, daunorubicin, dasatinib, vincristine, paclitaxel and oxaliplatin).

Our findings underscore the varied expression pattern of DME genes in cancer cells and TME components, highlighting their potential as biomarkers for selecting appropriate chemotherapy agents.

Personalized psycho-oncology represents a major challenge for the holistic care of cancer patients. It focuses on individualized psychotherapeutic and psychiatric interventions to address specific psychological needs. This narrative review summarizes the current literature on personalized psycho-oncology and highlights the prevalence and impact of psychiatric/psychological disorders in cancer patients. Personalized approaches, including tailored interventions and interdisciplinary collaboration, have been shown to be effective in improving mental health and overall quality of life. The integration of inflammatory biomarkers into treatment plans is a promising but challenging way to alleviate mental health problems. In addition, there is a need for specific diagnostic tools and treatment guidelines that take into account the specific psychological impact of different types of cancer. Future research should aim to refine these personalized strategies, improve diagnostic accuracy, and evaluate the cost-effectiveness of these interventions to improve both the psychological well-being and treatment outcomes of cancer patients.

Despite all major advancements in drug discovery and development in the pharmaceutical industry, cancer is still one of the most arduous challenges for the scientific community. The implications of nanotechnology have certainly resolved major issues related to conventional anticancer modalities; however, the undesired recognition of nanoparticles (NPs) by the mononuclear phagocyte system (MPS), their poor stability in biological fluids, premature release of payload, and low biocompatibility have restricted their clinical translation. In recent decades, chitosan (CS)-based nanodelivery systems (eg, polymeric NPs, micelles, liposomes, dendrimers, conjugates, solid lipid nanoparticles, etc.) have attained promising recognition from researchers for improving the pharmacokinetics and pharmacodynamics of chemotherapeutics. However, the specialty of this review is to mainly focus on and critically discuss the targeting potential of various CS-based NPs for treatment of different types of cancer. Based on their delivery mechanisms, we classified CS-based NPs into stimuli-responsive, passive, or active targeting nanosystems. Moreover, various functionalization strategies (eg, grafting with polyethylene glycol (PEG), hydrophobic substitution, tethering of stimuli-responsive linkers, and conjugation of targeting ligands) adapted to the architecture of CS-NPs for target-specific delivery of chemotherapeutics have also been considered. Nevertheless, CS-NPs based therapeutics hold great promise for improving therapeutic outcomes while mitigating the off-target effects of chemotherapeutics, a long-term safety profile and clinical testing in humans are warranted for their successful clinical translation.

Liquid biopsy is rapidly becoming an indispensable tool in the oncologist's arsenal; however, this technique remains elusive in a publicly funded healthcare system, and real-world evidence is needed to demonstrate utility and feasibility. Here, we describe the first experience of an in-house point of care liquid biopsy program at a Canadian community hospital. A retrospective review of consecutive cases that underwent plasma-based next-generation sequencing (NGS) was conducted. Liquid biopsy was initiated at the discretion of clinicians. Sequencing followed a point of care workflow using the Genexus™ integrated sequencer and the Oncomine precision assay, performed by histotechnologists. Results were reported by the attending pathologist. Eligible charts were reviewed for outcomes of interest, including the intent of the liquid biopsy, results of the liquid biopsy, and turnaround time from blood draw to results available. A total of 124 cases, with confirmed or suspected cancer, underwent liquid biopsy between January 2021 and November 2023. The median turnaround time for liquid biopsy results was 3 business days (range 1-12 days). The sensitivity of liquid biopsies was 71%, compared to tissue testing in cases with matched tissue results available for comparison. Common mutations included EGFR (29%), in 86 lung cancer patients, and PIK3CA (22%), identified in 13 breast cancer patients. Healthcare providers ordered liquid biopsies to inform diagnostic investigations and treatment decisions, and to determine progression or resistance mechanisms, as these reasons often overlapped. This study demonstrates that rapid in-house liquid biopsy using point of care methodology is feasible. The technique facilitates precision treatment and offers many additional advantages for cancer care.

This review explores the convergence of clinical radiotherapy and space radiation therapeutics, focusing on ionizing radiation (IR)-generated reactive oxygen species (ROS). IR, with high-energy particles, induces precise cellular damage, particularly in cancer treatments. The paper discusses parallels between clinical and space IR, highlighting unique characteristics of high-charge and energy particles in space and potential health risks for astronauts. Emphasizing the parallel occurrence of ROS generation in both clinical and space contexts, the review identifies ROS as a crucial factor with dual roles in cellular responses and potential disease initiation. The analysis covers ROS generation mechanisms, variations, and similarities in terrestrial and extraterrestrial environments leading to innovative ROS-responsive delivery systems adaptable for both clinical and space applications. The paper concludes by discussing applications of personalized ROS-triggered therapeutic approaches and discussing the challenges and prospects of implementing these strategies in clinical radiotherapy and extraterrestrial missions. Overall, it underscores the potential of ROS-targeted delivery for advancing therapeutic strategies in terrestrial clinical settings and space exploration, contributing to human health improvement on Earth and beyond.

Immunotherapy has transformed cancer treatment. Nevertheless, given the heterogeneity of clinical efficacy, the multiplicity of treatment options available and the possibility of serious adverse effects, selecting the most effective treatment has become the greatest challenge. Molecular imaging offers an attractive way for this purpose. ImmunoPET provides specific imaging with positron emission tomography (PET) using monoclonal antibodies (mAb) or its fragments as vector. By combining the high targeting specificity of mAb and the sensitivity of PET technique, immunoPET could noninvasively and dynamically reveal tumor antigens expression and provide theranostic tools of several types of malignancies. Because of their slow kinetics, mAbs require radioelements defined by a consistent half-life. Zirconium 89 (89Zr) and Copper 64 (64Cu) are radiometals with half-lives suitable for mAb labeling. Radiolabeling with a radiometal requires the prior use of a bifunctional chelate agent (BFCA) to functionalize mAb for radiometal chelation, in a second step. There are a number of BFCA available and much research is focused on antibody functionalization techniques or on developing the optimum chelating agent depending the selected radiometal. In this manuscript, we present a critical account of radiochemical techniques with radionuclides 89Zr and 64Cu and their applications in preclinical and clinical immuno-PET imaging.

Predictive biomarkers are essential for personalized medicine since they select the best treatment for a specific patient. However, of all biomarkers that are evaluated, only few are eventually used in clinical practice. Many promising biomarkers may be erroneously abandoned because they are investigated in small studies using standard statistical techniques which can cause small sample bias or lack of power. The standard technique for failure time endpoints is Cox proportional hazards regression with a multiplicative interaction term between binary variables of biomarker and treatment. Properties of this model in small studies have not been evaluated so far, therefore we performed a simulation study to understand its small sample behavior. As a remedy, we applied a Firth correction to the score function of the Cox model and obtained confidence intervals (CI) using a profile likelihood (PL) approach. These methods are generally recommended for small studies of different design. Our results show that a Cox model estimates the biomarker-treatment interaction term and the treatment effect in one of the biomarker subgroups with bias, and overestimates their standard errors. Bias is however reduced and power is increased with Firth correction and PL CIs. Hence, the modified Cox model and PL CI should be used instead of a standard Cox model with Wald based CI in small studies of predictive biomarkers.

In the last decades, carbonic anhydrases (CAs) have become the top investigated innovative pharmacological targets and, in particular, isoforms IX and XII have been widely studied due to the evidence of their overexpression in hypoxic tumors. The frantic race to find new anticancer agents places the quick preparation of large libraries of putative bioactive compounds as the basis of a successful drug discovery and development programme. In this context, multi-component and, in general, one-step reactions are becoming very popular and, among them, Biginelli's reaction gave clean and easy-to-isolate products. Thus, we synthesized a series of Biginelli's products (10-17a-b) and similar derivatives (20-21) bearing the benzenesulfonamide moiety, which is known to inhibit CA enzymes. Through the stopped-flow technique, we were able to assess their ability to inhibit the targeted CAs IX and XII in the nanomolar range with promising selectivity over the physiologically relevant isoforms I and II. Crystallography studies and docking simulations helped us to gain insight into the interaction patterns established in the enzyme-inhibitor complex. From a chemical similarity-based screening of in-house libraries of compounds, a diphenylpyrimidine (23) emerged. The surprisingly potent inhibitory activity of 23 for CAs IX and XII along with its strong antiproliferative effect on two (triple-negative breast cancer MDA-MB-231 and glioblastoma U87MG) cell lines laid the foundation for further investigation, again confirming the key role of CAs in cancer.

This comprehensive review delves into the pivotal role of the tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights into the intricate interplay between cancer cells and their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular and acellular elements, not only fosters tumor progression but also profoundly affects the efficacy of conventional and emerging cancer therapies. Through nuanced exploration, this review illuminates the multifaceted nature of the TME, elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, and the establishment of physical barriers to drug delivery. Moreover, it investigates innovative therapeutic approaches aimed at targeting the TME, including stromal reprogramming, immune microenvironment modulation, extracellular matrix (ECM)-targeting agents, and personalized medicine strategies, highlighting their potential to augment treatment outcomes. Furthermore, this review critically evaluates the challenges posed by the complexity and heterogeneity of the TME, which contribute to variable therapeutic responses and potentially unintended consequences. This underscores the need to identify robust biomarkers and advance predictive models to anticipate treatment outcomes, as well as advocate for combination therapies that address multiple facets of the TME. Finally, the review emphasizes the necessity of an interdisciplinary approach and the integration of cutting-edge technologies to unravel the intricacies of the TME, thereby facilitating the development of more effective, adaptable, and personalized cancer treatments. By providing critical insights into the current state of TME research and its implications for the future of oncology, this review highlights the dynamic and evolving landscape of this field.

Obstructive Sleep Apnoea (OSA) is a common heterogenous sleep disorder that is associated with a wide range of comorbidities and consequences, including the development of neurocognitive and cardiometabolic disorders. The heterogeneity of OSA necessitates a precision medicine approach to accurately diagnose this condition and to effectively manage patients. One of the primary models of precision medicine is described by the P4 approach of predicting those who are susceptible to disease, preventing the occurrence of disease, personalizing treatment, and encouraging patients to participate in their individual healthcare journey. Recent advances in oral appliance therapy and OSA monitoring techniques have fostered an exciting opportunity for enhanced collaboration between dentists and sleep physicians to optimize OSA precision medicine care. This review aims to discuss the sources of heterogeneity among OSA patients, provide an overview of the growing applications of oral appliance therapy and tailored monitoring programs for OSA that are shifting treatment to a more personalized and participatory model of care, and outline the pivotal role of dentists in managing patients with OSA.

Despite a comparatively favorable prognosis relative to other malignancies, breast cancer continues to significantly impact women's health globally, partly due to its high incidence rate. A critical factor in treatment failure is radiation resistance - the capacity of tumor cells to withstand high doses of ionizing radiation. Advancements in understanding the cellular and molecular mechanisms underlying radioresistance, coupled with enhanced characterization of radioresistant cell clones, are paving the way for the development of novel treatment modalities that hold potential for future clinical application. In the context of combating radioresistance in breast cancer, potential targets of interest include long non-coding RNAs (lncRNAs), micro RNAs (miRNAs), and their associated signaling pathways, along with other signal transduction routes amenable to pharmacological intervention. Furthermore, technical, and methodological innovations, such as the integration of hyperthermia or nanoparticles with radiotherapy, have the potential to enhance treatment responses in patients with radioresistant breast cancer. This review endeavors to provide a comprehensive survey of the current scientific landscape, focusing on novel therapeutic advancements specifically addressing radioresistant breast cancer.

Hecogenin (HCG), a steroidal sapogenin, possesses good antitumor properties. However, the application of HCG for cancer treatment has been hindered primarily by its moderate potency. In this study, we incorporated triphenylphosphonium cation (TPP+) at the C-3 and C-12 positions through different lengths of alkyl chains to target mitochondria and enhance the efficacy and selectivity of the parent compound. Cytotoxicity screening revealed that most of the target compounds exhibited potent antiproliferative activity against five human cancer cell lines (MKN45, A549, HCT-116, MCF-7, and HepG2). Structure-activity relationship studies indicated that the TPP+ group significantly enhanced the antiproliferative potency of HCG. Among these compounds, 3c demonstrated remarkable potency against MKN45 cells with an IC50 value of 0.48 μM, significantly more effective than its parent compound HCG (IC50 > 100 μM). Further investigations into the mechanism of action revealed that 3c induced apoptosis of MKN45 cells through the mitochondrial pathway. In a zebrafish xenograft model, 3c inhibited the proliferation of MKN45 cells. Overall, these results suggest that 3c, with potent antiproliferative activity, may serve as a valuable scaffold for developing new antitumor agents.

Novel immune and targeted therapies approved over the past 2 decades have resulted in dramatic improvements in cancer-specific outcomes for many cancer patients. However, many of these agents can induce cardiovascular toxicity in a subset of patients. The field of cardio-oncology was established based on observations that anti-neoplastic chemotherapies and mantle radiation can lead to premature cardiomyopathy in cancer survivors. While conventional chemotherapy, targeted therapy, and immune therapies can all result in cardiovascular adverse events, the mechanisms, timing, and incidence of these events are inherently different. Many of these effects converge upon the coronary microvasculature to involve, through endocardial endothelial cells, a more direct effect through close proximity to cardiomyocyte with cellular communication and signaling pathways. In this review, we will provide an overview of emerging paradigms in the field of Cardio-Oncology, particularly the role of the coronary microvasculature in mediating cardiovascular toxicity of important cancer targeted and immune therapies. As the number of cancer patients treated with novel immune and targeted therapies grows exponentially and subsequently the number of long-term cancer survivors dramatically increases, it is critical that cardiologists and cardiology researchers recognize the unique potential cardiovascular toxicities of these agents.

Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage.

We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis.

Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens.

Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.

Hematopoiesis, a process which generates blood and immune cells, changes significantly during mammalian development. Definitive hematopoiesis is marked by the emergence of long-term hematopoietic stem cells (HSCs). Here, we will focus on the post-transcriptional differences between fetal liver (FL) and adult bone marrow (ABM) HSCs. It remains unclear how or why exactly FL HSCs transition to ABM HSCs, but we aim to leverage their differences to revive an old idea: in utero HSC transplantation. Unexpectedly, the expression of certain RNA-binding proteins (RBPs) play an important role in HSC specification, and can be employed to convert or reprogram adult HSCs back to a fetal-like state. Among other features, FL HSCs have a broad differentiation capacity that includes the ability to regenerate both conventional B and T cells, as well as innate-like or unconventional lymphocytes such as B-1a and marginal zone B (MzB) cells. This chapter will focus on RNA binding proteins, namely LIN28B and IGF2BP3, that are expressed during fetal life and how they promote B-1a cell development. Furthermore, this chapter considers a potential clinical application of synthetic co-expression of LIN28B and IGF2BP3 in HSCs.

Cancer has become a serious health burden that results in high incidence and mortality rates every year, mainly due to various molecular alterations inside the cell. Liver X receptors (LXRs) dysregulation is one among them that plays a vital role in cholesterol metabolism, lipid metabolism and inflammation and also plays a crucial role in various diseases such as obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), cardiovascular diseases, Type 2 diabetes, osteoporosis, and cancer. Studies report that the activation of LXRs inhibits cancer growth by inhibiting cellular proliferation, inducing apoptosis and autophagy, regulating cholesterol metabolism, various signalling pathways such as Wnt, and PI3K/AKT, modulating the expression levels of cell-cycle regulators, and promoting antitumor immunity inside the tumor microenvironment. In this review, we have discussed the role, structure, and functions of LXRs and also summarized their ligands along with their mechanism of action. In addition, the role of LXRs in various cancers, tumor immunity and tumor microenvironment (TME) along with the importance of precision medicine in LXR-targeted therapies has been discussed to emphasize the LXRs as potent targets for the development of novel cancer therapeutics.

Gender and geographic access to care play a large role in health disparities in esophageal cancer care. The aim of our study was to evaluate disparities in peri-operative outcomes for patients undergoing esophagectomy based on gender and geographic location.

A retrospective cohort of prospectively collected data from patients who underwent esophagectomy from 2003 to 2022 was identified and analyzed based on gender and county, which were aggregated into existing state-level "metropolitan" versus "rural" designations. The demographics, pre-operative treatment, surgical complications, post-operative outcomes, and length of stay (LOS) of each group were analyzed using chi-squared, paired t-tests and single-factor ANOVA.

Of the 1545 patients, men (83.6%) and women (16.4%) experienced similar rates of post-operative complications, but women experienced significantly longer hospital (p = 0.002) and ICU (p = 0.03) LOSs as compared with their male counterparts, with no differences in 30-day mortality. When separated by geographic criteria, rural women were further outliers, with significantly longer hospital LOSs (p < 0.001) and higher rates of ICU admission (p < 0.001).

Rural female patients undergoing esophagectomy were more likely to have a longer inpatient recovery process compared with their female metropolitan or male counterparts, suggesting a need for more targeted interventions in this population.