Expert Review of Anticancer Therapy最新文献

Introduction: Managing urothelial carcinoma with immune checkpoint inhibitors requires addressing issues beyond clinical outcomes. Implementation difficulties affect most patients, predictive biomarkers show limited utility, and treatment discontinuation from toxicity remains problematic.

Areas covered: This article integrates clinical trials, systematic reviews, health-system evaluations, and guidelines from 2016 to 2025. We detail limitations of programmed death-ligand 1 (PD-L1) expression, panel-based tumor mutational burden (TMB), clinic-ready toxicity pathways, immune-appropriate response criteria (iRECIST), pseudoprogression, hyperprogression, post-ICI sequencing (FGFR3 alterations, enfortumab vedotin-based therapy, chemotherapy, trials), and delivery models (navigation, electronic patient-reported outcomes, telemedicine, payment structures).

Expert opinion: Optimizing systemic frameworks for immunotherapy care requires careful evaluation of functional status, protocols for immune-related adverse events management, standardization for assessments of clinical responses, and ensuring equitable access to care. ctDNA and AI-assisted radiomics are promising adjuncts to clinical care, but still require multi-center prospective validation before adoption into routine practice.

Introduction: Despite the introduction of several novel agents, survival for patients with metastatic gastric or gastroesophageal junction adenocarcinoma remains limited. In human epidermal growth factor receptor 2 (HER-2) positive disease, pembrolizumab plus trastuzumab and fluoropyrimidine- and platinum-based chemotherapy has recently demonstrated a survival benefit, particularly in tumors expressing programmed death-ligand 1 (PD-L1) with a combined positive score (CPS) ≥1 in the phase III KEYNOTE-811 trial.

Areas covered: This review summarizes the evolution of HER2-directed therapies in gastric cancer and focuses on the efficacy and safety of pembrolizumab in combination with trastuzumab and chemotherapy. We highlight the mechanistic rationale for dual HER2 and PD-1 blockade, pivotal trial evidence, and other novel HER2-directed therapies currently under active clinical evaluation in the first-line setting. A literature search was conducted using PubMed and ClinicalTrials.gov.

Expert opinion: Pembrolizumab plus trastuzumab and chemotherapy has established a new first-line standard of care for patients with HER2-positive, PD-L1 CPS ≥1 metastatic gastric or gastroesophageal junction adenocarcinoma. Nonetheless, primary and acquired resistance driven by HER2 heterogeneity, immune evasion, and dynamic molecular evolution remain major challenges. Next-generation HER2-targeted therapies, including bispecific antibodies, novel antibody - drug conjugates, and dual HER2 antibodies will be crucial to further improve outcomes in this population.

Introduction: Bladder cancer (BC) is associated with high recurrence and progression rates that require intensive surveillance. In this context, Artificial Intelligence (AI) offers promising tools to enhance diagnostic, prognostic, and surgical pathways.

Areas covered: This narrative review critically examines the current state of AI applications across the bladder cancer care focusing on diagnostic, prognostic and surgical domains. A comprehensive literature search was conducted to identify relevant studies. Key topics include radiomics in computed tomography (CT) and magnetic resonance imaging (MRI), radiogenomics, pathomics and AI-assisted cystoscopy. Furthermore, the role of AI in preoperative planning, intraoperative navigation and surgical training is discussed highlighting its integration in robotic and endoscopic procedures.

Expert opinion: AI is rapidly redefining bladder cancer management through multimodal data integration and predictive modeling. While current evidence demonstrates high diagnostic and prognostic performance, clinical implementation remains limited by heterogeneity, lack of standardization and insufficient external validation. Future efforts should prioritize prospective validation, explainability and integration into clinical workflows to realize AI's full potential in personalized uro-oncology.

Introduction: Liquid biopsy has emerged as an important approach to capture tumor-derived material from blood and other body fluids, offering a minimally invasive window into cancer biology. In non - small cell lung cancer (NSCLC), it enables comprehensive molecular profiling that informs patient management, from guiding therapy choices to monitoring disease status and assessing minimal residual disease (MRD).

Areas covered: Its main advantages over tissue biopsy lie in being noninvasive, capable of reflecting tumor heterogeneity and real-time biological changes. These strengths allow liquid biopsy to be applied at different clinical timepoints, including diagnosis, treatment decision-making, evaluation during therapy, detection of resistance, and surveillance for recurrence. Although circulating tumor DNA (ctDNA) remains the most established analyte, the scope is broadening to include circulating RNAs, circulating tumor cells, exosomes, DNA methylation signatures, and tumor-educated platelets, each providing complementary insights. A literature search of PubMed, EMBASE, and Web of Science was conducted without restrictions, supplemented by screening reference lists and major oncology conference abstracts.

Expert opinion: While significant progress has been made integrating liquid biopsies in NSCLC, challenges persist, encompassing issues of standardization, cost, and clinical integration.

Introduction: Host factors may affect immune-related adverse events (irAE) during immune checkpoint inhibitor (ICI) therapy. We systematically reviewed studies on body composition (BMI, CT/DXA-defined sarcopenia, sarcopenic obesity) and physical activity (PA) in relation to irAE incidence and severity in ICI-treated adults.

Methods: PubMed, Embase, Scopus, and Web of Science were searched from inception to 15 December 2024. Eligible studies assessed baseline body composition and/or PA in relation to irAE. Risk of bias was evaluated using the NIH tool and QUIPS. Findings were synthesized using structured narrative methods.

Results: Seven studies (2,590 patients) were included. Two large cohorts found overweight/obese patients had higher odds of any-grade irAE (OR = 1.4-1.5); one disease-specific cohort found no association. One CT-based study showed higher irAE risk with sarcopenia (OR = 2.64) and more with sarcopenic obesity (OR = 5.50). Two studies on PA were conflicting: one found higher PA reduced severe irAE risk (OR = 0.19), another found no association.

Conclusions: Body composition and PA may help predict irAE in ICI-treated patients. Evidence is low to very low certainty: overweight/obesity may increase toxicity risk, higher PA may lower risk, and evidence for sarcopenia is limited. Standardized prospective studies are needed to confirm these associations.

Protocol registration: https://www.crd.york.ac.uk/PROSPERO identifier is CRD420251084119.

Background: Treatment for advanced non-small cell lung cancer (NSCLC) has shifted from chemotherapy to targeted therapy and immunotherapy. We aimed to evaluate the effects of these novel therapies on advanced NSCLC in real-world settings.

Research design and methods: We conducted a retrospective cohort study using the SEER database of patients with advanced NSCLC receiving systemic therapy. Patients were stratified into three periods: chemotherapy (1992-2002), targeted therapy (2003-2014), and immunotherapy (2015-2022). We used interrupted time series analysis to evaluate changes in overall survival rate and cancer-specific survival rate (CSSR).

Results: The analysis included 32,899 patients. Compared to chemotherapy (11.9 months), overall survival was significantly longer with targeted therapy (19.3 months) and immunotherapy (27.4 months). The 3-year CSSR increased by 0.36% and 0.89% per year following targeted therapy and immunotherapy, respectively. Adenocarcinoma showed sustained improvement in 3-year CSSR after targeted therapy (0.52% per year) and immunotherapy (0.83% per year), while squamous cell carcinoma showed no significant change. Most subgroups showed continuous survival improvement after immunotherapy.

Conclusion: The introduction of targeted therapy and immunotherapy has produced significant survival improvement in adenocarcinoma, with the most pronounced benefits in immunotherapy. Treatment efficacy varies across subgroups highlighting the need for further investigation to optimize personalized therapy.

Introduction: HER2 is mutated in 2-4% of non-small cell lung cancers (NSCLC) and is associated with poor prognosis. Tyrosine kinase inhibitors (TKIs) targeting HER2 have historically been hampered by insufficient efficacy against exon 20 insertion mutations and lack of specificity, resulting in off-target adverse events. Zongertinib is an oral, irreversible HER2-selective TKI that spares wild-type EGFR, thereby minimizing associated toxicities. Zongertinib was recently approved in the United States (accelerated), China (conditional), and Japan for patients with previously treated advanced HER2-mutant NSCLC.

Areas covered: This article outlines the discovery and clinical development of zongertinib that led to these approvals. We discuss the first-in-human Beamion LUNG-1 trial (NCT04886804), in which zongertinib demonstrated encouraging and durable activity, with a manageable safety profile, in patients with HER2-mutant advanced NSCLC. Finally, we summarize ongoing clinical trials of zongertinib, including its assessment as first-line treatment for advanced HER2-mutant NSCLC.

Expert opinion: Zongertinib is the first oral TKI approved for HER2-mutant NSCLC and will provide patients with a convenient, tolerable and effective treatment option in an area of significant unmet need. Next steps include its potential transition to a first-line setting, identification of additional indications, and development of novel combination regimens.

Introduction: Peripheral neuropathy is a well-known complication in patients undergoing taxane chemotherapy. Several measures to prevent this condition have been tried, but none have yielded conclusive results.

Methods: MEDLINE, Embase, Cochrane, and Web of Science databases were searched for randomized (RCTs) and self-controlled (SCTs) trials comparing cryotherapy with standard care in patients with breast cancer undergoing taxane-based chemotherapy and reporting any of the following outcomes: (1) chemotherapy-induced peripheral neuropathy (CIPN) or (2) adverse events.

Results: A total of 395 patients from 10 studies were included, all female. The age of participants ranged from 49.8 to 56.1 years. Incidence of any-grade CIPN was not significantly different between groups (RCTs RR 0.59; 95% CI 0.21-1.66; p = 0.320; SCTs RR 0.40; 95% CI 0.10-1.62; p = 0.198). No difference was observed in adverse events leading to discontinuation of cryotherapy (RCTs RR 0.72; 95% CI 0.17-3.05; p = 0.660; SCTs RR 1.09; 95% CI 0.51-2.34; p = 0.821).

Conclusions: Cryotherapy was not statistically superior to the standard of care in reducing CIPN, without an increased risk of adverse events leading to discontinuation of cryotherapy. These findings underscore the need for further studies with more rigorous methodologies to definitively validate or rule out this finding.

Registration: PROSPERO (CRD420251018990).

Introduction: Adipokines are bioactive signaling molecules secreted from adipose tissue (AT) that have regulatory functions in maintaining metabolic homeostasis. In physiological conditions, balanced adipokine secretion supports metabolic stability and organ function. However, disruption of this balance can promote chronic inflammation and increase cancer risk. While their role in normal physiology is recognized, biological functions of adipokines in renal cell carcinoma (RCC) remain partially understood.

Areas covered: This review explores the biological functions of key adipokines such as adiponectin, leptin, visfatin, nesfatin-1, apelin, and omentin-1 in normal cellular processes and RCC. A search of the literature on PubMed, Web of Science, and Embase databases was performed from January 2000 through April 2025. This review summarizes findings on how these adipokines influence tumor biology, with a specific focus on their emerging roles in RCC. The review includes new findings and their possible limitations and the complexity of adipokine signaling and their roles in promoting or inhibiting tumorigenesis.

Expert opinion: The current evidence highlights adipokines as promising mediators in RCC biology; however, their mechanisms of action remain unclear. Further mechanistic studies are essential to unravel how adipokines regulate tumor initiation and progression. Without such understanding, the rational design of targeted therapies remains limited.

Introduction: Neuroplasticity is a dynamic process by which the brain reorganizes its structure and function in response to internal and external stimuli. In patients with brain neoplasms, neuroplasticity is crucial for preserving or restoring function, as it enables compensation for the tumor-induced disruption of neuronal circuits. Understanding this adaptive capacity is vital for improving clinical outcomes.

Areas covered: This review examines current research on neuroplasticity in the context of brain tumors. It explores how factors such as tumor location, molecular and genetic profiles, cognitive reserve, and DNA repair capacity influence neural adaptation. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, focusing on studies related to neuroplasticity, connectome analysis, and artificial intelligence (AI) in neuro-oncology. The application of connectomics is discussed as a means to assess brain network reorganization. Furthermore, the integration of AI is analyzed concerning its potential in enhancing diagnostic precision, prognostic models, and individualized treatment strategies.

Expert opinion: The convergence of neuroplasticity research, connectomics, and AI offers promising avenues for advancing personalized neuro-oncology care. Greater understanding of these elements can guide clinicians in developing tailored therapeutic interventions, ultimately improving patient function, prognosis, and quality of life.