Expert Review of Anticancer Therapy最新文献

Background: Patients with advanced EGFR-mutant NSCLC and high PD-L1 expression (TPS ≥50%) typically respond poorly to EGFR-TKI monotherapy. We compared EGFR-TKI plus chemotherapy versus TKI alone in this population.

Research design and methods: This retrospective study included 212 patients receiving first-line osimertinib with chemotherapy (n = 98) or as monotherapy (n = 114). Primary endpoint was progression-free survival (PFS).

Results: Combination therapy significantly improved median PFS overall (22.5 vs 13.8 months; HR = 0.513, 95% CI:0.372-0.803; p < 0.001) and in PD-L1-high patients (18.2 vs 7.9 months; HR = 0.356, 95% CI:0.195-0.641; p = 0.001). ORR was higher with combination therapy (67.3% vs 36.8%; p < 0.001). Grade ≥3 adverse events were more common with combination therapy (45.9% vs 22.8%) but were primarily manageable hematological events.

Conclusions: Osimertinib-chemotherapy combination showed superior efficacy versus monotherapy in EGFR-mutant, PD-L1-high NSCLC, with manageable safety. Our real-world findings validate and extend the FLAURA2 results by highlighting this high-risk subgroup as one that may derive particular benefit from first-line combination therapy.

Introduction: Lung cancer remains the leading cause of cancer-related mortality, and reliable prognostic biomarkers are needed. The prognostic significance of myeloid-derived suppressor cells (MDSCs) in lung cancer is the aim of the current systematic review and meta-analysis.

Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase, and eligible studies included patients with lung cancer reporting survival/progression outcomes by MDSCs level. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist. The Comprehensive Meta-Analysis (CMA) software version 3 was used to estimate pooled hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: Twenty-five studies (1,679 patients) were included. Elevated baseline monocytic MDSCs (M-MDSCs) were significantly associated with worse overall survival (OS) in non-small cell lung cancer (NSCLC) (HR = 1.89, 95% CI: 1.39-2.59) and small cell lung cancer (SCLC) (HR = 2.72, 95% CI: 1.62-4.59), and with shorter progression/recurrence-free survival in NSCLC (HR = 1.86, 95% CI: 1.44-2.40). Associations for polymorphonuclear MDSCs (PMN-MDSCs) were weaker and inconsistent, showing significance only in HR for OS based on univariable data (HR = 1.76, 95% CI: 1.32-2.35).

Conclusions: High M-MDSCs predict adverse outcomes in lung cancer, supporting their role as prognostic biomarkers and potential therapeutic targets.

Registration: PROSPERO (CRD420251026405).

Introduction: Intravesical sequential gemcitabine - docetaxel (Gem/Doce) has emerged as an important chemotherapeutic regimen in the management of non - muscle-invasive bladder cancer (NMIBC). It holds particular clinical significance in the context of high-risk NMIBC (HR-NMIBC) that either fails standard Bacillus Calmette - Guérin (BCG) immunotherapy or when BCG is contraindicated or unavailable. The combination leverages two cytotoxic agents with complementary mechanisms to achieve tumor eradication while aiming to preserve the bladder.

Areas covered: This review explores the evidence for the use of intravesical Gem/Doce in NMIBC. We performed a scoping review of studies across BCG-naïve and BCG-unresponsive populations (MEDLINE, Embase, ClinicalTrials.gov; 2015-2025). Outcomes assessed included efficacy, adverse events, safety, and bladder preservation. We also discuss emerging data on novel delivery methods, maintenance strategies and combination regimens.

Expert opinion: Intravesical Gem/Doce has transitioned from an experimental salvage approach to a promising mainstream option in NMIBC management. Current evidence indicates that intravesical Gem/Doce can achieve durable disease control in a substantial proportion of patients with HR-NMIBC, offering a well-tolerated and cost-effective bladder-sparing strategy. While the absence of randomized trials means Gem/Doce is not yet a formal standard of care, the accumulating clinical experience and supportive outcomes have led to its inclusion in contemporary treatment algorithms.

Background: To explore Ubiquitin D (UBD) and autophagy in hepatocellular carcinoma (HCC) and the key role of Olaparib targeting UBD in treating HCC.

Research design and methods: Bioinformatics analysis was conducted to study UBD expression in HCC tissues. qRT-PCR and Western blot measured UBD mRNA/protein levels, autophagy markers, and Gln metabolism proteins in HCC tissues. Cellular thermal shift assay (CETSA) confirmed Olaparib-UBD interaction. A xenograft tumor model was established to observe tumor growth in mice, with qRT-PCR and western blot used to measure UBD expression levels in tumor tissues and Immunohistochemistry (IHC) used to assess expression of Microtubule-associated protein light chain 3 (LC3), sequestosome 1 (P62), solute carrier family 1 member 5 (SLC1A5), and glutaminase (GLS).

Results: UBD was highly expressed in HCC tissues (p = 7.6e-11). UBD could negatively regulate autophagy levels by activating Gln metabolism. Olaparib could target and downregulate UBD expression, promoting HCC cell autophagy by regulating Gln metabolism pathways. Olaparib treatment in xenograft mice overexpressing UBD significantly reduced tumor growth (p < 0.05), inhibited Gln metabolism pathways, and enhanced HCC cell autophagy.

Conclusions: Olaparib targeted UBD to promote autophagy in HCC by inhibiting Gln metabolism pathways.

Introduction: Non-muscle invasive bladder cancer (NMIBC) is a malignancy with a significant recurrence and progression risk. While intravesical Bacillus Calmette-Guérin (BCG) has remained the standard of care for decades, limitations in efficacy, tolerability, and global supply underscore the need for novel therapeutic strategies. Many patients relapse after BCG and are offered radical cystectomy, a highly morbid operation which some are unfit for or decline. Immune checkpoint inhibitors (ICIs) have revolutionized neoadjuvant and advanced bladder cancer therapy. This has driven interest in ICIs as bladder-sparing alternatives in BCG-unresponsive high-risk NMIBC (HR-NMIBC).

Areas covered: This scoping review (MEDLINE, Embase, ClinicalTrials.gov; 2015-2025) explores the emerging role of ICIs in NMIBC. It summarizes data from completed and ongoing trials in both BCG-naïve and BCG-unresponsive settings, highlighting key efficacy and safety outcomes. Special emphasis is given to combination approaches and novel delivery routes.

Expert opinion: Checkpoint inhibition represents a potentially transformative advance in the bladder-sparing management of NMIBC, particularly in patients unfit for or refusing radical cystectomy. However, widespread adoption will require robust phase III data combined with optimal patient selection to temper concerns regarding toxicity and cost. Ongoing research into combination regimens and local delivery may refine risk-benefit profiles and personalize treatment in the near future.

Background: Desmoid tumors are rare, locally aggressive tumors that are often life-affecting with a significant burden on afflicted patients. While systemic therapy for progressive disease is often preferred, there is a paucity of studies comparing disease control rates of agents based on tumor location or other disease-related factors.

Methods: Dual-center retrospective analysis of disease control in patients with intra-abdominal (IA) and extra-abdominal (EA) desmoid tumors who received liposomal doxorubicin (LD). Disease control rate (DCR) was defined as stable disease (if evidence of progression prior to LD therapy) or partial response.

Results: 54 patients were included, 38.9% (21/54) with IA desmoid tumors and 35.2% (19/54) with Familial Adenomatous Polyposis (FAP)-associated desmoid tumors. DCRs for patients with IA and EA desmoid tumors were 76.2% and 45.5%, respectively (odds ratio 3.80; p = 0.03). The DCR for patients with FAP-associated desmoid tumors was 73.7%, compared to 48.6% for those without FAP (odds ratio 2.96, p = 0.09). Mean times to next treatment were 80.5 weeks and 36.3 weeks for patients with and without FAP.

Conclusion: LD is effective and well-tolerated with a high potential for tumor control and prolonged duration of time until next treatment, especially in patients with FAP and IA desmoid tumors.

Introduction: Chromatin regulators (CRs) are critical in cancer development, yet their prognostic value in lung squamous cell carcinoma (LUSC) remains unclear. This study aimed to develop a CR-based prognostic model and explore the role of APOBEC1 in LUSC progression.

Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. Gene Ontology and KEGG pathway enrichment were performed. Prognostic CRs were identified using univariate Cox and Lasso analyses. Drug sensitivity was assessed via the Drug Signatures Database. Key CRs were validated by PCR. APOBEC1 expression and prognosis were evaluated through pan-cancer analysis and experimentally validated in LUSC cell lines using colony formation, CCK-8, wound healing, and transwell assays.

Results: An eight-gene CR-based signature was established, achieving 5-year AUCs of 0.87, 0.92, and 0.73 in the TCGA training, validation, and GEO datasets, respectively. High-risk patients showed enrichment in cancer-related pathways, greater immune infiltration, and elevated immune checkpoint expression. They were also more sensitive to Dasatinib, Bexarotene, and Bicalutamide. APOBEC1 was overexpressed across multiple cancer types and promoted proliferation and migration in LUSC cell lines.

Conclusions: This study presents a robust CR-based survival model and highlights APOBEC1 as a potential therapeutic target in LUSC.

Introduction: Urothelial carcinoma (UC) is marked by significant molecular heterogeneity and this complexity challenges precision medicine. Recent advances have improved biomarker development for UC diagnosis, prognosis and treatment.

Areas covered: This review discusses established and emerging biomarkers in UC, including FGFR3 and HER2 alterations, PD-L1 expression and circulating tumor DNA (ctDNA). It also summarizes novel biomarkers such as Nectin-4, TROP-2, HER3, tumor mutational burden (TMB), and interferon-gamma signatures. The expanding role of artificial intelligence in biomarker discovery and interpretation is also addressed. Current literature was reviewed by a systematic search using PubMed, focusing on high-impact clinical trials, guidelines and recent reviews published up to May 2025.

Expert opinion: Despite advances, clinical implementation of biomarkers in UC is limited by methodological inconsistencies and lack of standardization. Robust clinical trials and multi-modal approaches, including liquid biopsy, tissue analysis, and AI-driven tools, will be essential to advance precision oncology in UC.

Introduction: Understanding histological variants is crucial for accurate diagnosis and management of bladder cancer (BC). Most BCs are urothelial carcinomas (UC), which can evolve into aggressive histological variants (HVs) such as micropapillary, plasmacytoid, small-cell carcinoma, and sarcomatoid subtypes.

Areas covered: This review will focus on the clinicopathologic characteristics of the most common non-urothelial and other rare variants (signet-ring cell variant, decoy cells, osteoclastic giant cell variant) BCs, to be distinguished from BC variant histology containing a UC component. In addition, we reviewed the effects of understanding HVs in developing therapeutic and diagnostic methods for BC. Our analysis combines evidence from searches in PubMed/NCBI, Google Scholar, ClinicalTrials.gov, and key conference proceedings from 2011 to 2025.

Expert opinion: Recognizing and differentiating between various variant histology (VH) subtypes is crucial for tailoring treatment strategies and improving patient outcomes. Discovering and uniform reporting of variant histology in UC is essential. Clinical trials focusing specifically on patients with HVs are needed to evaluate the impact of new treatment modalities and optimize management strategies. More clinical studies with specific guidelines and goals, along with research, patient records, databases, and tissue banks, are needed to improve treatment plans and identify markers for patients with urinary tract cancer.