INTRODUCTION:Fertility preservation is an increasingly important component of survivorship care for adolescent and young adult (AYA) women with central nervous system (CNS) tumors. As survival improves, attention to long-term reproductive health is increasingly needed. AREAS COVERED:This narrative review examines how CNS tumors and their treatments may impair fertility, including hypothalamic-pituitary dysfunction, spinal irradiation, and chemotherapy-induced ovarian toxicity, particularly from alkylating agents. Established fertility preservation strategies, including oocyte and embryo cryopreservation, and emerging approaches are discussed, together with the limited evidence on the reproductive effects of newer neuro-oncology therapies and the management of pregnancy after CNS tumor diagnosis. A PubMed search of literature published up to March 2026 was performed, including prospective and retrospective studies, systematic reviews, meta-analyses, clinical guidelines, and relevant case reports addressing fertility preservation and pregnancy in women with CNS tumors. EXPERT OPINION:Early oncofertility counseling and individualized fertility risk assessment should be integrated into routine neuro-oncology care before potentially gonadotoxic treatments. Multidisciplinary management and long-term reproductive follow-up are essential to support informed reproductive decisions, while prospective studies are needed to clarify the reproductive effects of newer therapies and the impact of pregnancy on CNS tumor behavior.
INTRODUCTION:Gestational trophoblastic neoplasia (GTN) comprises a group of rare malignant disorders arising from placental trophoblastic tissue. Despite the remarkable chemosensitivity of high-risk GTN, delays in diagnosis, inadequate risk stratification, or inappropriate chemotherapy regimens remain the primary determinants of adverse outcomes. Understanding the role of chemotherapy is essential to ensure optimal management, maximize cure rates, and ultimately eliminate preventable mortality associated with this disease. AREAS COVERED:A narrative review of the literature was conducted using PubMed/MEDLINE, Scopus, and Web of Science, from database inception through July 2026, supplemented by manual review of reference lists and international guidelines. Study selection was based on clinical relevance, methodological rigor, and contribution to the understanding of chemotherapy strategies in high-risk disease. The evidence was qualitatively synthesized, focusing on risk stratification, first-line and salvage chemotherapy, treatment outcomes, mechanisms of chemoresistance, emerging therapies, and the management of relapsed disease. EXPERT OPINION:Although multiagent chemotherapy remains the cornerstone of treatment, future advances in molecular diagnostics, predictive biomarkers, targeted therapies, and immunotherapy, together with continued centralization of care, have the potential to further personalize treatment, reduce toxicity, and improve outcomes.
INTRODUCTION:Pediatric oncology poses distinct scientific, ethical, regulatory, and commercial challenges compared to adult oncology. Although survival rates for certain childhood malignancies have improved significantly, progress in relapsed, refractory, and rare pediatric cancers remains limited. AREAS COVERED:A comprehensive literature search was performed using major biomedical databases, including PubMed, Scopus, and Web of Science. Historically, pediatric drug development followed adult approvals, resulting in significant delays in access to innovative therapies. Recent pediatric regulatory reforms have shifted requirements from indication-based approaches toward mechanism-of-action-based evaluation, promoting earlier and more biologically relevant pediatric investigation. This report examines the biological differences between pediatric and adult cancer populations, reviews the evolution of pediatric oncology from a regulatory perspective, identifies the principal scientific and operational barriers limiting progress, and outlines strategic pathways to accelerate the development of safe and effective therapies for children with cancer. EXPERT OPINION:Despite meaningful therapeutic advances, pediatric oncology drug development remains constrained by small patient populations, biological divergence from adult malignancies, long-term safety considerations, and limited commercial incentives. Overcoming these challenges will require global collaboration, regulatory alignment, innovative trial design, and a deliberate focus on child-specific tumor biology rather than extrapolating from adult oncology paradigms.
INTRODUCTION:Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but produced immune-related adverse events across multiple organs. Renal toxicities are uncommon yet significant, and secondary serum amyloid A (AA) amyloidosis has emerged as a rare, underrecognized complication reflecting sustained systemic inflammation rather than direct immune-mediated kidney injury. AREAS COVERED:This review summarizes evidence on AA amyloidosis as a renal adverse event of checkpoint inhibition, drawing on case reports, a systematic pharmacovigilance (FAERS) analysis, and mechanistic extrapolation from AA amyloidosis biology and cytokine signaling. Proposed mechanisms linking PD-1/PD-L1 blockade to cytokine activation, hepatic amyloid A production, and deposition are discussed as hypotheses rather than confirmed pathways. Clinical features, diagnostic challenges, and outcomes are characterized, emphasizing limits of creatinine-based monitoring, biopsy's importance, and limited reversibility once nephrotic syndrome develops. EXPERT OPINION:ICI-associated AA amyloidosis is a severe, inflammation-driven toxicity likely underdiagnosed. Management remains empirical, grounded in mechanistic rationale and case experience rather than trials, often ineffective once nephrotic syndrome is established. Greater awareness, early nephrology referral, and a low threshold for biopsy should become routine for ICI-treated patients with unexplained proteinuria. Evidence remains scarce (11 cases, 26 pharmacovigilance reports), so recommendations reflect expert opinion pending validation; causality with amyloidogenesis remains unestablished.
INTRODUCTION:Angiosarcoma is a rare and aggressive vascular malignancy characterized by substantial clinical and molecular heterogeneity. Grouping UV-associated cutaneous, radiation-associated, and visceral tumors within unselected clinical trials may obscure treatment effects in biologically distinct subgroups. AREAS COVERED:This narrative review examines cytotoxic and anti-angiogenic therapy, immunotherapy, oncolytic virotherapy, non-canonical vascular targets, and advances in multiomic, spatial, and proteomic profiling. It also evaluates adaptive and Bayesian trial designs as strategies for biomarker-enriched development. Literature was identified through PubMed and AI-assisted discovery, with relevant clinical trial reports, conference abstracts, and regulatory guidance included through July 2026. EXPERT OPINION:Current systemic therapies provide modest population-level benefit and generally limited durability. Emerging evidence supports biologically distinct treatment-responsive subsets, including selected UV-associated cutaneous and secondary angiosarcomas, although validated predictive biomarkers remain lacking. Progress will require integration of molecular, immune, spatial, and protein-level features into patient selection. Adaptive and enrichment-based trial designs may reduce dilution of subgroup-specific signals and support the transition from histology-defined cohorts toward mechanistically stratified treatment.
INTRODUCTION:Thyroid cancer is the most common endocrine malignancy, and despite advances in understanding its genomic drivers, significant challenges remain in predicting tumor behavior, therapeutic response, and disease progression. This review summarizes advances in transcriptomic profiling and liquid biopsy approaches that are reshaping molecular classification, biomarker discovery, and precision management of thyroid cancer. AREAS COVERED:This review examines recent advances in tissue- and liquid biopsy-based transcriptomic approaches for thyroid cancer, including bulk RNA sequencing, single-cell and spatial transcriptomics, extracellular vesicle RNAs, circulating tumor cells, and circulating non-coding RNAs, together with their applications in molecular classification, biomarker discovery, tumor heterogeneity, disease monitoring, therapeutic stratification, and precision oncology. The review also discusses emerging multi-omics integration and challenges in clinical translation. Literature was identified through systematic searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, supplemented by TCGA, GEO, and ClinicalTrials.gov, covering publications from January 2000 to June 2026. EXPERT OPINION:Transcriptomic profiling is poised to redefine thyroid cancer management by moving beyond static morphologic classification toward biologically informed precision medicine through improved molecular classification, risk stratification, therapeutic selection, and longitudinal disease monitoring. However, routine clinical implementation will require standardized methodologies, prospective multicentre validation, and integration with liquid biopsy, multi-omics, and artificial intelligence-driven analytical frameworks.
INTRODUCTION:Anal squamous cell carcinoma (SCC) is a rare cancer. Metastatic anal SCC is still a significant clinical challenge due to limited treatment options and poor outcomes. AREAS COVERED:This review paper will focus on retifanlimab, a humanized monoclonal antibody targeting the programmed cell death protein 1 (PD-1) pathway, and its role in the treatment of metastatic anal SCC, both as monotherapy or in combination with chemotherapy. This review will evaluate its efficacy, safety, and place within the current therapeutic landscape. EXPERT OPINION:The POD1UM-303 trial is the first randomized phase III study for patients with metastatic and locally, advanced unresectable anal SCC. The results from POD1UM-303 are practice-changing, establishing retifanlimab in combination with carboplatin and paclitaxel as a new standard of care for first-line treatment in this setting. Current research includes investigating earlier integration of PD-(L)1 inhibitors with definitive chemoradiotherapy in the locally advanced setting. Further biomarker-driven studies are essential to guide treatment and improve patient selection.
INTRODUCTION:Portal vein resection (PVR) has become an established component of pancreatic cancer surgery for selected patients with portal vein-superior mesenteric vein involvement. Although advances in surgical techniques and multidisciplinary treatment have improved perioperative outcomes, whether PVR itself independently improves long-term survival remains controversial. AREAS COVERED:This review summarizes the historical evolution of PVR, critically evaluates contemporary evidence regarding its safety and oncological outcomes, and examines the methodological limitations that prevent definitive conclusions regarding its independent survival benefit. We further discuss pathological venous invasion as a marker of aggressive tumor biology and review the emerging concept of biological resectability, incorporating neoadjuvant treatment response, serum CA19-9 dynamics, circulating tumor DNA, molecular profiling, and artificial intelligence into patient selection for surgery. EXPERT OPINION:The value of PVR should no longer be judged solely by technical feasibility or anatomical resectability. Instead, portal vein invasion should be interpreted as both an anatomical and biological finding, and indications for PVR should be guided by integrated biological assessment within a multidisciplinary treatment strategy. Future progress will depend on identifying patients most likely to derive meaningful oncological benefit through biologically informed precision surgical oncology.
INTRODUCTION:Biliary tract cancer (BTC) is a biologically heterogeneous and highly aggressive malignancy with limited therapeutic options and poor survival. Although chemotherapy, targeted therapies, and immune checkpoint inhibitors have improved treatment outcomes, intrinsic and acquired resistance remain the major barriers to durable clinical benefit. AREAS COVERED:A comprehensive literature search of PubMed, Embase, and Web of Science was conducted for studies published through June 2026. This narrative review summarizes current mechanisms of therapeutic resistance in BTC, including genetic evolution, clonal selection, epigenetic plasticity, cancer stem cells, non-genetic adaptive resistance, metabolic reprogramming, and tumor microenvironment-mediated immune evasion. Emerging strategies to overcome resistance are discussed, including rational combination therapies based on acquired vulnerability, next-generation targeted therapies, tumor microenvironment remodeling, immunotherapy optimization, epigenetic and metabolic interventions, and precision oncology supported by liquid biopsy and dynamic molecular monitoring. EXPERT OPINION:BTC management is evolving toward biologically informed precision oncology. Integrating comprehensive molecular profiling, longitudinal liquid biopsy, biomarker-guided patient selection, and mechanism-based combination therapies will enable dynamic treatment adaptation and may improve long-term outcomes. Advances in multi-omics, artificial intelligence, and biomarker-driven clinical trial designs are expected to further accelerate personalized therapeutic strategies.
INTRODUCTION:Acute myeloid leukemia (AML) is an aggressive hematologic cancer that accounts for approximately one third of all newly diagnosed leukemias annually in the United States (US), and is associated with high mortality and substantial clinical, economic and patient burden. AREAS COVERED:Prior reviews have explored AML disease burden from isolated epidemiological, treatment, or cost perspectives. In this narrative review, we integrate the published evidence identified through targeted searches of PubMed and Google Scholar conducted between June 2025 and July 2026. Literature published between 2006 and 2026 addressing the epidemiologic, clinical, economic and humanistic burden of AML was reviewed to characterize unmet needs across the continuum of care, from diagnosis and treatment selection to patient outcomes including remission, relapse, and death. EXPERT OPINION:Significant unmet needs persist across all burden dimensions, particularly for older patients and those ineligible for intensive chemotherapy. Therefore, expanded access to targeted therapies, oral regimens, and supportive care models has the potential to enhance health-related quality of life and reduce 'time toxicity/burden' for patients. The multifaceted aspects of AML burden necessitate a treatment approach that balances safety and efficacy with patient preference and patient-centered value, to optimize outcomes for patients, caregivers, and healthcare systems.
BACKGROUND:Serum Ca 19-9 is the most widely used biomarker in pancreatic ductal adenocarcinoma (PDAC). This study assessed the link between preoperative Ca 19-9, neoadjuvant chemotherapy (ChTNeo), and outcomes after pancreatic resection. RESEARCH DESIGN AND METHODS:We retrospectively analyzed 378 patients with PDAC who underwent resection. Patients were grouped by preoperative Ca 19-9: elevated (>37 U/mL; N = 320) or normal (≤37 U/mL; N = 58). ChTNeo was administered to 99 patients (30.9%) in the elevated group and 35 (60.3%) in the normal group. RESULTS:Local recurrence, distant metastases, and mortality were significantly more frequent in patients with elevated Ca 19-9, while progression-free and overall survival were shorter. Patients with normal Ca 19-9 had excellent outcomes regardless of ChTNeo. Patients with elevated preoperative Ca 19-9 and ChTNeo administration had significantly better outcomes than those undergoing upfront surgery. CONCLUSIONS:Normal preoperative Ca 19-9 identifies a group with a favorable prognosis after PDAC resection. Elevated preoperative Ca 19-9 is associated with worse oncological outcomes. Among these patients, ChTNeo was associated with better treatment outcomes than upfront surgery; however, because baseline Ca 19-9 levels before ChTNeo were unavailable, these findings should not be interpreted as evidence that elevated baseline Ca 19-9 predicts benefit from neoadjuvant chemotherapy.
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 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 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 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 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 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: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.
