Pancreatic ductal adenocarcinoma (PDAC) remains a formidable malignancy with rising incidence and dismal long-term survival, largely due to late-stage presentation and intrinsic resistance to therapy. Recent advances in the multidisciplinary management of PDAC have reshaped treatment paradigms across disease stages. For localized disease, innovations in surgical techniques and the adoption of neoadjuvant strategies have improved resection rates and survival outcomes. In metastatic settings, multiagent chemotherapy regimens and precision therapies targeting BRCA mutations and rare gene fusions are expanding treatment options. Immunotherapeutic modalities, including checkpoint inhibitors, adoptive cell therapies, and mRNA vaccines, show emerging promise despite PDAC’s traditionally immunosuppressive microenvironment. This review synthesizes the current evidence on established therapies and critically evaluates novel and investigational approaches poised to redefine the therapeutic landscape of pancreatic cancer.

Background: With rising obesity rates, pharmacological interventions are increasingly used in non-diabetic adults. While being effective in managing weight, these agents frequently cause gastrointestinal (GI) side effects, affecting adherence and long-term outcomes. Objective: To systematically evaluate the frequency, severity, and types of GI adverse effects (AEs) associated with anti-obesity medications in obese adults without diabetes. Methods: Following PRISMA 2020 guidelines, PubMed, Google Scholar, BMJ, and Web of Science were searched (last search July 2025). Eligible studies included randomized controlled trials, non-randomized trials, cohort studies, cross-sectional, and case–control studies. Only reports of GI AEs in non-diabetic adults were included. Risk of bias was assessed using Cochrane RoB 2 and Newcastle–Ottawa scales. Results: Out of 733 articles screened, 12 studies met predefined inclusion criteria, including one large cohort of 18,386 participants, along with randomized and observational trials of smaller size. The most frequently reported GI symptoms were nausea, vomiting, diarrhea, and constipation, predominantly with GLP-1 receptor agonists such as semaglutide and tirzepatide, especially during dose escalation. Orlistat commonly linked to steatorrhea and flatulence, while phentermine was associated with reduced GI motility. Newer agents, including retatrutide and orforglipron, also demonstrated notable GI side effect profiles. Natural products and investigational agents reported fewer adverse events but lacked long-term data and standardized reporting. Limitations: Evidence was limited by heterogeneity in study design and inconsistent reporting of GI outcomes. Conclusion: GI side effects are common across anti-obesity medications, particularly GLP-1 receptor agonists. Although generally mild to moderate, these symptoms can impact adherence and lead to treatment discontinuation. Tailored titration schedules, proactive patient counseling, and standardized adverse event reporting may improve tolerability. Further research is warranted to evaluate long-term GI outcomes and compare safety across emerging pharmacologic agents.

The advent of targeted therapies has significantly transformed the management of non-small-cell lung cancer (NSCLC), improving survival across all disease stages. Discoveries of both common and rare oncogenic drivers are advancing rapidly, posing a challenge for clinicians and researchers to remain up to date in this dynamic field. This review highlights the evolving landscape of therapeutic strategies for actionable mutations in lung cancer, with particular attention given to the latest developments in KRAS-targeted treatments including non-G12C mutations, pan-RAS inhibitors, and agents targeting RAS-GTP. We also examine the existing standards of care for NSCLC harboring EGFR and ALK alterations, as well as emerging therapies poised for clinical use. Additional discussion includes advancements in therapies directed at MET, HER2, RET, ROS1, and FGFR alterations—each representing promising targets in NSCLC. This review concludes by exploring the growing evidence surrounding TROP-2 as a novel therapeutic target, especially relevant in cases where previous targeted treatments have failed.

Gastroesophageal cancer (GEC) represents a global health burden, with rising incidence and high mortality. Despite advancements in early detection and systemic therapies, outcomes remain poor, especially in advanced stages. Management requires a multidisciplinary, multimodal approach that integrates surgery, chemotherapy, radiotherapy, targeted agents, and immunotherapy, tailored by tumor histology, location, and molecular profile. For localized disease, perioperative chemotherapy or chemoradiotherapy is standard, with adjuvant immunotherapy now emerging in selected high-risk cases. In metastatic or unresectable settings, systemic therapy forms the backbone of treatment, with biomarker-driven regimens targeting HER2, PD-L1, MSI-H/dMMR, and CLDN18.2, offering improved outcomes. Novel agents and combinations, including bispecific antibodies, FGFR2 inhibitors, and immunotherapy-based strategies, are actively being explored in clinical trials. This review provides a comprehensive overview of the evolving therapeutic landscape of GEC. It emphasizes the growing role of precision medicine and the integration of emerging clinical data into practice.

Background/Objectives: Metabolic syndrome is a prevalent global health concern characterized by central obesity, insulin resistance, hypertension, and dyslipidemia. Growing evidence suggests that metabolic dysregulation may influence prostate cancer risk and disease behavior; however, findings across studies remain inconsistent. This systematic review aimed to evaluate the association between metabolic syndrome and prostate cancer risk, clinicopathologic characteristics, and disease outcomes. Methods: A systematic literature search was conducted in PubMed/MEDLINE from database inception through the final search update on 10 January 2026, with supplementary searches of Google Scholar, Wiley Online Library, the Clinical Oncology journal collection, and reference lists. Observational studies assessing the relationship between metabolic syndrome and prostate cancer outcomes were eligible for inclusion. Two reviewers independently screened titles and abstracts, followed by full text review to determine eligibility. Discrepancies were resolved through consensus. Risk of bias was assessed using design-specific tools, including the Newcastle–Ottawa Scale, Cochrane Risk of Bias 2 tool, and Joanna Briggs Institute checklist. Findings were synthesized narratively because of heterogeneity in study design, metabolic syndrome definitions, populations, outcomes, and effect estimates. Results: A total of 1304 records were identified across all databases. After duplicate assessment, records underwent title and abstract screening, followed by full text assessment. Twenty-four studies, ranging from small clinic-based cohorts to large population-based cohorts exceeding 5 million participants, met the inclusion criteria and were included in the qualitative synthesis. Most studies were cohort or case–control designs conducted in North America, Europe, and Asia. Overall, evidence for a uniform association between composite metabolic syndrome and prostate cancer incidence was inconsistent. Associations appeared more suggestive for clinically significant, high-grade, or adverse pathological features, although findings varied by study design, metabolic syndrome definition, detection context, and adjustment level. Several studies suggested that individual components of metabolic syndrome, particularly obesity and insulin resistance, may be key drivers of these associations. Conclusions: Available evidence suggests a heterogeneous relationship between metabolic syndrome, related metabolic abnormalities, and prostate cancer outcomes. Evidence for a uniform association with overall prostate cancer incidence was inconsistent, whereas signals were more frequently reported for clinically significant, high-grade, or adverse pathological features. However, these findings should be interpreted cautiously because of observational study designs, heterogeneous MetS definitions, detection context, and variable adjustment. Further well-designed prospective studies are needed to clarify temporality, causal pathways, and the contributions of individual metabolic components.

Background and Clinical Significance: Congenital erythropoietic porphyria (CEP), also known as Günther disease, is a rare autosomal recessive porphyria caused by a deficiency of uroporphyrinogen III synthase, leading to the accumulation of phototoxic type I porphyrins. CEP classically presents in infancy with severe photosensitivity, blistering, scarring, and hemolytic anemia; however, significant phenotypic variability has increasingly been recognized. Case Presentation: We report a 32-year-old woman diagnosed with CEP in early infancy who demonstrated persistently and profoundly elevated erythrocyte porphyrin levels over more than a decade, yet who followed a relatively non-mutilating clinical course. Genetic testing identified a low-penetrance intronic UROS variant typically associated with erythropoietic protoporphyria, underscoring diagnostic challenges and genotype–phenotype discordance. The patient experienced marked improvement in photosensitivity and burning pain after initiation of afamelanotide, without the need for transfusion therapy or stem cell transplantation. Conclusions: This case highlights the heterogeneity of CEP, the importance of long-term biochemical follow up, and the potential role of afamelanotide in improving quality of life for selected patients with CEP.