INTRODUCTION: The therapeutic landscape for metastatic prostate cancer has expanded substantially over the last decade, yet treatment selection remains predominantly driven by clinical parameters rather than validated mo...INTRODUCTION: The therapeutic landscape for metastatic prostate cancer has expanded substantially over the last decade, yet treatment selection remains predominantly driven by clinical parameters rather than validated molecular predictors. This review addresses the urgent need to refine patient stratification by critically examining emerging and established predictive biomarkers that may enable a precision medicine approach in advanced disease. AREAS COVERED: This review provides a comprehensive overview of predictive biomarkers in metastatic prostate cancer, including androgen receptor aberrations, mismatch repair deficiency, SPOP mutations, TMPRSS2/ERG fusions, PTEN/PI3K/AKT pathway alterations, and novel therapeutic targets such as STEAP1, DLL3, TROP-2, and Nectin-4. We discuss their biological underpinnings, mechanistic relevance, and clinical evidence supporting their potential predictive role across treatment settings. A structured literature search was conducted using PubMed/MEDLINE and major international oncology congress databases, focusing on peer-reviewed publications and clinical trial reports published up to February 2026, with particular emphasis on prospective and biomarker-driven studies. EXPERT OPINION: While several molecular alterations show compelling biological rationale and encouraging clinical signals, few biomarkers have achieved prospective validation sufficient for routine implementation. The next phase of progress will depend on biomarker-enriched trial designs, harmonized testing strategies, and integration of multi-omic profiling to overcome biological heterogeneity and therapeutic resistance.
INTRODUCTION: Rising cancer incidence disproportionately affects low- and middle-income countries (LMICs). Brachytherapy (BT), a form of radiotherapy (RT), is an important modality in the treatment of cervical cancer and...INTRODUCTION: Rising cancer incidence disproportionately affects low- and middle-income countries (LMICs). Brachytherapy (BT), a form of radiotherapy (RT), is an important modality in the treatment of cervical cancer and prostate cancer. Given its unique resource requirements, barriers to the use of BT are present, especially in LMIC settings. AREAS COVERED: This nonsystematic review aims to describe the role of BT in the treatment of cervical and prostate cancer, discuss barriers in the implementation and use of BT in LMIC settings, share suggested solutions, and highlight cases from global settings. Barriers are discussed in categories including infrastructure, financial, geographic, and human resources and training. Cases presented highlight barriers and facilitators to implementing BT. EXPERT OPINION: With BT a required component of treatment for locally advanced cervical cancer, and an important treatment modality in prostate cancer, understanding the barriers present to BT and the impact on real-world outcomes, is crucial. A critical part of ongoing research will be the continued study of resource-stratified guidelines for brachytherapy and particularly image guidance. The cases presented here may serve as models for other settings, with the goal of increasing access to this essential treatment modality for patients around the globe.
INTRODUCTION: Schlafen11 (SLFN11) has emerged as a powerful biomarker of sensitivity to DNA-damaging agents in various cancers. However, not much is known about its role in brain tumors. Conflicting reports show that it...INTRODUCTION: Schlafen11 (SLFN11) has emerged as a powerful biomarker of sensitivity to DNA-damaging agents in various cancers. However, not much is known about its role in brain tumors. Conflicting reports show that it is a biomarker for response to cisplatin and a prognostic factor in some brain tumors, such as medulloblastomas, but can even be a negative prognostic factor in others, like glioblastomas. AREAS COVERED: In this review, we discuss what is known about the various roles of SLFN11 in cancer, with special attention to brain tumors. Specifically, we focus on the seemingly dual role of SLFN11 in brain tumors; positive prognostic in some and negative in others. Additionally, we describe some glioma cases with high SLFN11 expression, often showing aggressive presentation, a good response to initial treatment, and subsequent widespread relapse. EXPERT OPINION: In brain tumors such as medulloblastomas and primary central nervous system lymphomas (PCNSL), when total cell killing can be expected by chemotherapy and/or chemoradiotherapy, high SLFN11 expression is a positive prognostic marker. However, SLFN11 can also be highly expressed in mesenchymal tumors, and in cases where total cell killing cannot be achieved, widespread relapse can accompany an initial response.
BACKGROUND: Lung cancer remains the most significant cause of cancer-related death worldwide due to the critical challenges in diagnosis. Despite the promising efforts, the existing models faced challenges in capturing t...BACKGROUND: Lung cancer remains the most significant cause of cancer-related death worldwide due to the critical challenges in diagnosis. Despite the promising efforts, the existing models faced challenges in capturing the complex patterns in medical imaging data while minimizing the computational complexity. In this research, the lung cancer detection using Computed Tomography (CT) images is performed using the Reverse Task attention-enabled Distributed Elman convolutional neural Network (RTsDEN) model that helps in mitigating the challenges in existing methods and improving the detection performance for real-time applications. RESEARCH DESIGN AND METHODS: The proposed model, combining the Reverse Task attention-(RTsAt) module and the distributed Elman concept, significantly contributes to capturing the intricate disease patterns from the complex backgrounds and varying environmental conditions. In addition, the proposed method exploits the adaptive lobe and multigranular nodule segmentation stage to facilitate better understanding and interpretation for accurate diagnosis. RESULTS: Experimental results reveal that the proposed RTsDEN outperforms other existing models by attaining 97.12% accuracy, 98.03% precision 96.22% recall using LUNA 16 dataset and 97.72% accuracy, 98.31% precision, 97.14% recall using the LIDC-IDRI dataset. CONCLUSION: The research introduces an efficient DL model with an ensemble approach, which significantly influences effective lung cancer detection.
INTRODUCTION: Endometrial cancer is the most frequently diagnosed gynecologic malignancy. Despite favorable clinical outcomes associated with early-stage disease, advanced or recurrent endometrial cancer is significantly...INTRODUCTION: Endometrial cancer is the most frequently diagnosed gynecologic malignancy. Despite favorable clinical outcomes associated with early-stage disease, advanced or recurrent endometrial cancer is significantly more aggressive and coincides with inauspicious survival rates. AREAS COVERED: Since endometrial cancer often develops in patients with obesity and type 2 diabetes, studies have evaluated metformin as a treatment for this neoplasm. Alternatively, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which mimic the GLP-1 peptide, may confer a decreased risk for endometrial cancer and represent a novel and promising anti-neoplastic therapy. In the current mini-review, we recount the preclinical results abstracted from studies identified via the PUBMED database from 2016-2026, with an emphasis on GLP-1 RAs in the treatment of endometrial cancer. EXPERT OPENION: Preclinical data suggest that GLP-1 RAs avert progesterone resistance, augment the effects of hormone therapy, and prevent chemoresistance, not to mention bestow a substantive benefit in the adjuvant treatment of endometrial cancer. Currently, however, the results associated with GLP-1 RAs in treating malignancies are preliminary and warrant further investigation with randomized clinical trials.
INTRODUCTION: Early-onset gastrointestinal (GI) cancers, defined as those diagnosed before the age of 50, are increasing worldwide, whereas the incidence of late-onset GI cancers has stabilized or declined. These trends...INTRODUCTION: Early-onset gastrointestinal (GI) cancers, defined as those diagnosed before the age of 50, are increasing worldwide, whereas the incidence of late-onset GI cancers has stabilized or declined. These trends highlight the need to better understand age-related differences in disease biology and risk factors. METHODS: This narrative review compares early- and late-onset GI malignancies. We discuss differences in epidemiology, molecular and genetic features, clinical presentation, and management strategies. Relevant literature was identified through a non-systematic search of PubMed and additional sources, and selected according to scientific relevance and quality. Publications from 2000 to March 2026 were reviewed, with inclusion of selected landmark historical studies when appropriate. RESULTS: Early-onset tumors are more frequently diagnosed at advanced stages and may reflect the impact of early-life environmental exposures, metabolic dysregulation, and microbiome alterations. Although they share several molecular features with late-onset disease, younger patients often present distinct clinical and survivorship needs, including genetic counseling and fertility preservation. Current treatment strategies remain largely similar across age groups due to limited age-specific evidence. CONCLUSION: Early-onset GI cancers should be understood within an age-specific biological and environmental framework. Improved understanding of these tumors may support better prevention, earlier diagnosis, and more personalized management strategies.
INTRODUCTION: Metastatic prostate cancer is a leading cause of global cancer-related mortality. Contemporary treatment strategies are increasingly guided by genomic analyses, which are typically performed on archival or...INTRODUCTION: Metastatic prostate cancer is a leading cause of global cancer-related mortality. Contemporary treatment strategies are increasingly guided by genomic analyses, which are typically performed on archival or newly obtained biopsies. Nevertheless, tissue biopsies in this context face significant technical and clinical challenges. Circulating tumor DNA (ctDNA) testing from peripheral blood is a promising approach that addresses many of these limitations and enables sequential testing. AREAS COVERED: This review examines the evidence for ctDNA in prostate cancer management and considers where it may be most effectively integrated into clinical practice. We discuss the strengths and limitations of ctDNA-based diagnostics, the key principles guiding clinical interpretation, and future directions, including novel applications under development in clinical trials. EXPERT OPINION: In the metastatic castration-resistant prostate cancer (mCRPC) setting, ctDNA genomic profiling is an established method to identify patients eligible for PARP inhibitor therapy, and an emerging biomarker for prognostication, treatment selection, and response assessment. The results of ongoing clinical trials will inform on the future role of ctDNA for prostate cancer.
INTRODUCTION: The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed substantially with the introduction of androgen receptor pathway inhibitors (ARPIs), which have improved survival...INTRODUCTION: The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed substantially with the introduction of androgen receptor pathway inhibitors (ARPIs), which have improved survival outcomes and raised the threshold for demonstrating additional benefit from local interventions. In this setting, the role of local treatment of the primary tumor remains clinically relevant but requires reassessment, taking into account modern systemic intensification. AREAS COVERED: This expert opinion discusses the current role of local treatment of the primary tumor in mHSPC patients eligible for ARPIs therapy, focusing on prostate radiotherapy and surgery. It examines the evidence supporting radiotherapy in the androgen deprivation therapy era, the uncertainties emerging in the ARPI era, the implications for toxicity and local symptom control, and the rationale for ongoing trials evaluating local treatment in combination with contemporary systemic therapy. EXPERT OPINION: In the ARPI era, local treatment should be considered within an individualized, multidisciplinary framework rather than as an automatic standard for patients with mHSPC. Its main value may increasingly lie in preventing local progression and genitourinary complications in selected patients, while a definitive overall survival benefit on top of intensified systemic therapy remains unproven.
INTRODUCTION: Precision oncology has transformed cancer care by enabling biomarker-guided therapeutic strategies; however, durable clinical benefit remains limited across many tumor types. Emerging evidence suggests that...INTRODUCTION: Precision oncology has transformed cancer care by enabling biomarker-guided therapeutic strategies; however, durable clinical benefit remains limited across many tumor types. Emerging evidence suggests that treatment failure cannot be fully explained by static genomic alterations alone, but rather reflects dynamic interactions among tumor evolution, host biology, and therapeutic and healthcare system pressures. AREAS COVERED: This narrative review examines the biological, technological, clinical, and systemic barriers limiting the effectiveness of precision oncology. We summarize literature identified from PubMed, MEDLINE, and Web of Science (2015-2026), focusing on therapeutic resistance, tumor microenvironment dynamics, longitudinal molecular monitoring, predictive biomarkers, multi-omics integration, adaptive trial design, implementation science, and healthcare disparities. We also discuss emerging concepts in evolutionary oncology, non-genetic resistance mechanisms, phenotypic plasticity, and host genomic variability that influence treatment response and disease progression. EXPERT OPINION: Precision oncology is undergoing a paradigm shift from static mutation-based treatment selection toward adaptive, longitudinal, and systems-oriented cancer management. The key limitation is no longer identification of actionable alterations alone, but the inability to integrate tumor evolution, host factors, and real-time biomarker dynamics into clinical decision-making. Future progress will depend on longitudinal molecular monitoring, adaptive therapeutic sequencing, integrated tumor-host frameworks, and equitable learning healthcare systems.
INTRODUCTION: Antibody-drug conjugates (ADCs) are rapidly expanding across solid tumors, but their toxicity profiles remain heterogeneous and clinically challenging. This review addresses the need for practical, standard...INTRODUCTION: Antibody-drug conjugates (ADCs) are rapidly expanding across solid tumors, but their toxicity profiles remain heterogeneous and clinically challenging. This review addresses the need for practical, standardized approaches to identifying and managing ADC-related adverse events. AREAS COVERED: We summarize the mechanisms underlying ADC toxicity, focusing on EMA-approved agents and their most frequent or severe adverse events, including ILD/pneumonitis, ocular toxicity, neutropenia, diarrhea, skin reactions, and hyperglycemia. We combine evidence from pivotal trials, regulatory documents, and emerging literature with practical clinical experience. The review includes operational algorithms and flowcharts designed to support real-world decision-making. Literature was identified through PubMed and EMBASE searches, regulatory Summary of Product Characteristics (SmPCs), and key phase I-III clinical trials up to January 2025. EXPERT OPINION: Improving ADC tolerability will require earlier identification of high-risk patients, structured toxicity-monitoring pathways, and molecular innovations such as Fc engineering, linker optimization, and probody or bispecific ADC formats. Integrating predictive tools, including AI-based radiomics, may further reduce toxicity and expand the therapeutic index.
Gonzalez-Fierro A, Chavez-Blanco A, Dominguez-Gomez G
… +7 more, Romo-Pérez A, Pastrana-Peralta P, Gutierrez-Delgado F, Kast RE, Correa-Basurto J, Cortes-Algara A, Duenas-Gonzalez A
INTRODUCTION: Cancer treatment is predominantly guided by the Somatic Mutation Theory (SMT), which focuses on highly selective drugs targeting driver mutations. This approach has transformed outcomes in specific cancers,...INTRODUCTION: Cancer treatment is predominantly guided by the Somatic Mutation Theory (SMT), which focuses on highly selective drugs targeting driver mutations. This approach has transformed outcomes in specific cancers, including chronic myeloid leukemia, advanced melanoma, renal cell carcinoma, and HER2-positive breast cancer. However, its overall impact remains limited: cancer drug development has an approximately 5.2% success rate, with a median overall survival benefit of only 2.8 months across 124 FDA-approved drugs (374 indications) from 2003 to 2021. These limitations underscore the need for complementary strategies. AREAS COVERED: This narrative review examines three interrelated concepts in cancer care: Polypharmacy: concurrent use of multiple drugs for different conditions in one patient. Polypharmacology: design of single drugs that engage multiple molecular targets within one disease, often via multitarget-directed ligands (MTDLs) to disrupt redundant pathways and delay resistance. Polypharmacotherapy: simultaneous use of multiple (often repurposed non-oncology) drugs to target diverse pathways in a cancer patient. EXPERT OPINION: Polypharmacy requires optimization to minimize risks. Polypharmacology should advance through computational design of balanced MTDLs. Polypharmacotherapy provides a pragmatic and equitable complement to SMT-based precision oncology. Urgent clinical trials are needed to validate this approach, overcome commercial and structural barriers, and improve treatment efficacy, accessibility, and equity worldwide.
BACKGROUND: Warfarin dosing in cancer patients is challenging due to altered pathophysiology and variable responses. While machine learning offers predictive potential, clinical adoption requires interpretability. This s...BACKGROUND: Warfarin dosing in cancer patients is challenging due to altered pathophysiology and variable responses. While machine learning offers predictive potential, clinical adoption requires interpretability. This study is an initial attempt at addressing whether different dosing strategies are required in this vulnerable population. RESEARCH DESIGN AND METHODS: This observational study analyzed 1,746 patients (124 with cancer) from the International Warfarin Pharmacogenetics Consortium database. Five machine learning algorithms were developed and compared with the best-performing model interpreted using SHAP analysis. Bayesian Additive Regression Trees provided uncertainty quantification, and the Virtual Twins method estimated cancer's individualized treatment effect on dose requirements. RESULTS: Genetic variants, particularly VKORC1 and CYP2C9, dominated dose prediction in both cohorts. However, cancer introduced complexity: clinical predictors showed greater variability and prediction errors, while Bayesian analysis revealed wider uncertainty intervals for inaccurate estimates. The Virtual Twins method demonstrated substantial heterogeneity in cancer's effect, with mean individualized treatment effect of 3.35 mg/week, yet 62.5% of patients exhibited positive effects indicating higher dose requirements. These findings suggest uniform dose adjustments for cancer patients may be inappropriate. CONCLUSIONS: Cancer patients possibly require personalized warfarin dosing, as genetic and clinical factors interact unpredictably. Explainable artificial intelligence and Bayesian models potentially enable individualized anticoagulation in oncology.
INTRODUCTION: Delayed methotrexate elimination (DME) is observed in ~15% of treatment cycles in patients with cancer receiving high-dose methotrexate (HDMTX). Given the strong association between DME and nephrotoxicity,...INTRODUCTION: Delayed methotrexate elimination (DME) is observed in ~15% of treatment cycles in patients with cancer receiving high-dose methotrexate (HDMTX). Given the strong association between DME and nephrotoxicity, oncologists might benefit from the input of a nephrologist/medical oncologist with a focus on nephrology when assessing and planning treatment for patients requiring HDMTX. AREAS COVERED: Identifying patients who are at risk of DME and related acute kidney injury (AKI), and developing a bespoke assessment and monitoring plan (with a focus on kidney assessment and monitoring), may help to reduce the risk of complications and enable the continuation of HDMTX treatment, hopefully optimizing long-term survival outcomes. EXPERT OPINION: In this perspective article, based on a search of PubMed literature and expert opinion, we explore the definition and causes of DME and AKI, and the impact of these on patients receiving HDMTX, and examine the key risk factors and early indicators of DME and AKI. A pathway with a nephrology focus is suggested for the assessment, monitoring, and treatment of patients with or at risk of DME.
INTRODUCTION: Immunotherapy with immune checkpoint inhibitors (ICIs) has become an important component of cervical cancer treatment, leading to improved outcomes in selected patient populations. However, despite recent a...INTRODUCTION: Immunotherapy with immune checkpoint inhibitors (ICIs) has become an important component of cervical cancer treatment, leading to improved outcomes in selected patient populations. However, despite recent approvals, prognosis in recurrent or metastatic disease remains poor and the immunotherapy landscape is rapidly evolving with the development of novel agents and combination strategies. AREAS COVERED: This scoping review maps emerging ICI-based strategies in cervical cancer, focusing on novel targets, next-generation programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) antibodies, bispecific antibodies and combination regimens. Ongoing phase I-II interventional clinical trials were identified through ClinicalTrials.gov and the European Union Clinical Trials Register from database inception to 1 February 2026. Fifty-nine clinical trials were included in the analysis. Evidence was synthesized descriptively and organized thematically. The final protocol was registered in the Open Science Framework (https://osf.io/swdz9/overview). EXPERT OPINION: The expanding role of ICIs across multiple disease stages suggests that most patients with cervical cancer will be exposed to ICIs during their treatment course. However, widespread clinical implementation is limited by a lack of validated predictive biomarkers, cost considerations and toxicity management. Future progress will depend on biomarker-driven trial designs, rational combination strategies and studies addressing optimal sequencing and immunotherapy rechallenge.
AIMS: To gather information regarding treatment patterns, outcomes, and healthcare resource utilization (HCRU) for patients with advanced/metastatic triple-negative breast cancer (TNBC) in real-world clinical settings in...AIMS: To gather information regarding treatment patterns, outcomes, and healthcare resource utilization (HCRU) for patients with advanced/metastatic triple-negative breast cancer (TNBC) in real-world clinical settings in Japan. METHODS: From commercially available health claims databases, patients diagnosed with TNBC between April 2008 and August 2015 were categorized into those initially diagnosed with early-stage (Stage I-IIIB) TNBC who underwent surgery with or without perioperative treatments and subsequently experienced recurrence, and those initially diagnosed at Stage IV. RESULTS: Among the 276 and 490 patients in the recurrence and Stage IV cohorts, systemic treatments were prescribed to 147 (53.3%) and 190 (38.8%) patients, respectively. Commonly used first-line treatments included capecitabine (20.4%), tegafur-gimeracil-oteracil (19.0%), and bevacizumab + paclitaxel (10.9%) (recurrence cohort); and bevacizumab + paclitaxel (19.5%), paclitaxel (12.1%), and 5-fluorouracil + epirubicin + cyclophosphamide (10.0%) (Stage IV cohort). Second- and third-line regimens were highly diverse. Time-to-treatment discontinuation decreased with advancing treatment lines. In the recurrence cohort without perioperative treatments, survival tended to be longer. Higher HCRU was observed with advancing treatment lines in the recurrence cohort, but not the Stage IV cohort. CONCLUSION: Treatments varied among Japanese patients diagnosed with recurrent and Stage IV disease. These data may inform future real-world studies.
INTRODUCTION: Despite major advances in the management of bladder cancer over the past decade, including practice-changing studies with immune checkpoint inhibitors and antibody drug conjugates (ADC), patients continue t...INTRODUCTION: Despite major advances in the management of bladder cancer over the past decade, including practice-changing studies with immune checkpoint inhibitors and antibody drug conjugates (ADC), patients continue to desire treatment strategies that not only improve survival but also allow them to retain their bladder. Trimodal therapy (TMT), consisting of maximal transurethral resection of bladder tumor (TURBT), radiation, and chemotherapy, remains an important option for appropriately selected patients. AREAS COVERED: We discuss the current standard of care for the management of localized bladder cancer with a focus on TMT including chemotherapy regimens used in TMT, the role of maximal TURBT, potential biomarkers, and the effect of histologic subtype on outcomes. We also provide updates on important upcoming trials that will hopefully translate into new treatment options. EXPERT OPINION: In appropriately selected patients, TMT is an alternative to radical cystectomy in the management of muscle invasive bladder cancer (MIBC). All patients with MIBC should be evaluated by a multidisciplinary team consisting of urology, medical oncology, and radiation oncology to determine the best treatment plan for an individual patient. Ongoing trials are studying new regimens to provide additional options for bladder preservation.