This systematic review aimed to synthesize experimental evidence on the anticancer effects of Lacticaseibacillus rhamnosus (L. rhamnosus) and its derivatives against colorectal cancer (CRC) cell models. Eligible studies investigated probiotics, postbiotics, or bioactive compounds derived from L. rhamnosus with an in vitro component; studies relying solely on in vivo animal models, clinical trials, or observational designs were excluded. PubMed and Scopus were searched to identify relevant studies. Risk of bias was assessed using a modified QUIN tool, and extracted data were tabulated. Owing to incomplete numerical data, meta-analysis was not feasible, and the results were synthesized accordingly. Seventeen studies were included. L. rhamnosus and its derivatives reduced CRC cell proliferation, induced apoptosis, and caused cell cycle arrest. Reported mechanisms included upregulation of Bax, caspase-3/9, and p53; downregulation of Bcl-2/Bcl-xl; inhibition of Wnt/β-catenin signaling; reduced invasion and migration; increased reactive oxygen species; and immunomodulatory effects. Key limitations were heterogeneity in interventions, dosages, exposure periods, and cell lines, along with incomplete reporting, which precluded quantitative synthesis. Overall, preclinical evidence indicates multimodal anticancer effects of L. rhamnosus in CRC models; however, standardized reporting and translational research are required.

Hand-foot skin reaction (HFSR) is a common adverse effect of vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), but its prognostic value remained disputable. In this study, we aimed to assess the association between HFSR and survival outcomes in cancer patients receiving VEGFR-TKIs. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched from inception to 29 June 2025. Two authors independently selected cohort studies, extracted data and appraised the risk of bias of included studies using the Quality In Prognosis Studies checklist. The outcomes were overall survival (OS) and progression-free survival (PFS). A random-effects model meta-analysis was performed to calculate pooled hazard ratio (HR) with 95% confidence intervals (CIs). Subgroup analyses based on various cancer types and VEGFR-TKIs types were also conducted. Thirty-two observational studies involving 6543 patients receiving VEGFR-TKIs were included, of whom 2671 experienced HFSR. Patients who developed VEGFR-TKI-induced HFSR showed better OS (HR 0.54, 95% CI 0.49-0.60) and PFS (HR 0.59, 95% CI 0.53-0.65) compared with those who did not. Subgroup analysis revealed significantly improved OS and PFS in patients with hepatocellular carcinoma, colorectal cancer or non-small cell lung cancer who developed VEGFR-TKI-induced HFSR. HFSR was also a positive prognostic factor for OS and PFS in patients receiving sorafenib, regorafenib, fruquintinib, anlotinib and cabozantinib. In conclusion, VEGFR-TKI-induced HFSR may serve as a positive surrogate marker for survival. Early detection and optimal management for HFSR in patients receiving VEGFR-TKI therapy is needed to maintain treatment efficacy and life quality. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42024598845.

The widespread clinical use of immune checkpoint inhibitors (ICIs) in oncology has been accompanied by an increased incidence of immune-related adverse events (irAEs). When ICIs are combined with other medications, the risk of drug-induced liver injury (DILI) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) may be amplified. Moxifloxacin, a fluoroquinolone antibiotic known to cause hepatic injury and cutaneous adverse reactions, is an uncommon culprit in the setting of prior ICI therapy but warrants vigilance for its potential to precipitate acute DILI and TEN.

Copyright: © 2026 Aleid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Locally advanced or metastatic urothelial carcinoma (la/mUC) is associated with poor prognosis and limited treatment options. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach. While previous meta-analyses have shown the efficacy and safety of ADCs in UC, the rapid development of new ADC agents and combination therapies necessitates an updated and comprehensive evidence synthesis.

Antiangiogenic combination therapy-antiangiogenic agents combined with immune checkpoint inhibitors and/or chemotherapy-has become an important treatment strategy for advanced driver-negative non-small cell lung cancer (NSCLC). We conducted a network meta-analysis to compare efficacy and safety and identify optimal antiangiogenic combinations.

Immune checkpoint inhibitors (ICPis) are associated with islet function impairment (IFI), manifesting as hyperglycemia, diabetes mellitus (DM), or diabetic ketoacidosis (DKA). Delayed detection and management may lead to irreversible β-cell damage and life-threatening complications. We conducted a systematic review and meta-analysis to assess the risk of IFI associated with ICPis.

Chemotherapy-related cognitive impairment (CRCI) is a prevalent and distressing issue among older adults with cancer, affecting quality of life and treatment adherence. While its mechanisms remain unclear, biomarkers have emerged as promising tools for understanding CRCI. This systematic review aimed to explore the relationships between cognitive impairment following chemotherapy and biomarkers in older patients with cancer.

Chemotherapy-related cardiac dysfunction (CTRCD) is a major limitation of cardiotoxic cancer therapies. Although global longitudinal strain (GLS) allows early detection of myocardial injury, preventive strategies remain scarce. Angiotensin receptor-neprilysin inhibitors (ARNIs) may offer cardioprotection, but current evidence is limited. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating Sacubitril/Valsartan versus control in patients undergoing chemotherapy. PubMed, Embase, and Cochrane databases were searched. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were computed for binary and continuous outcomes. Four randomized controlled trials comprising 412 participants were included; 42.7% received ARNI therapy, with follow-up ranging from 6 to 18 months. Compared with control, ARNI significantly preserved left ventricular systolic function (MD 1.47%, 95% CI 0.59-2.34) and attenuated GLS deterioration (MD -0.93%, 95% CI -1.49 to -0.38). However, ARNI did not significantly reduce the incidence of CTRCD (RR 0.40, 95% CI 0.08-1.97) or all-cause mortality (RR 0.63, 95% CI 0.08-5.01). ARNI increased the risk of hypotension but had no significant effects on NT-proBNP or dyspnea. In conclusion, ARNI therapy improves GLS and left ventricular ejection fraction during chemotherapy but has not yet demonstrated reductions in CTRCD or mortality. Hypotension remains a key safety consideration.

Renal impairment (RI), defined as estimated glomerular filtration rate less than 60 mL/min with or without the need for dialysis, is a frequent and severe complication in patients with relapsed/refractory multiple myeloma (RRMM), as it can affect patient prognosis, drug metabolism and treatment options. Although bispecific antibodies (BsAbs) have been approved in RRMM patients, their safety and efficacy in patients with RI remain insufficiently characterized, as most clinical trials excluded individuals with significant renal dysfunction. This systematic review was conducted in accordance with the PRISMA guidelines. PubMed, Scopus, and ScienceDirect were searched up to February 2, 2026, for clinical trials and retrospective real-world studies evaluating BsAbs in RRMM patients with reported data from patients with RI. Abstracts presented in major international scientific congresses over the preceding 3 years, including ASH, IMS, ASCO, EHA, EMN, were also systematically screened. A total of 11 eligible studies were identified, including 3 pivotal trials and 8 real-world cohorts, encompassing 1117 patients. ORR, PFS and OS were comparable between patients with and without RI. Safety profile, including incidence of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), infections and hematologic toxicities were also comparable across renal subgroups. Only the incidence of thrombocytopenia was significantly increased in patients with RI. Overall, BsAbs demonstrate substantial efficacy and manageable safety in RRMM patients with renal dysfunction. Outcomes were similar to those of patients with preserved renal function. These findings support the use of BsAbs in this high-risk population both in clinical practice and in future clinical trials.

PURPOSE: Osimertinib displays substantial inter-individual variability in both pharmacokinetics and pharmacodynamics. This study aimed to explore the exposure-response relationship of osimertinib, thereby to provide a basis for personalized therapeutic strategies. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and China Biology Medicine Literature Database separately through October 2024, with no study type restrictions. The Newcastle-Ottawa Scale was used for quality assessment, and data were extracted and recorded using Excel software. The meta-analysis was conducted using Stata software. RESULTS: A total of nine observational studies were included. Among them, five studies identified a correlation between steady-state trough concentration and progression-free survival, with three specifically demonstrating that the low steady-state trough concentration group had longer progression-free survival. One study observed a negative correlation between clearance and overall survival via Cox proportional hazards regression. Additionally, several studies reported correlations between exposure and adverse events, though conclusions varied substantially across studies. CONCLUSION: Multiple studies demonstrated that lower osimertinib steady-state trough concentration correlated with longer progression-free survival in Non-Small-Cell Lung Cancer, challenging the conventional assumption that higher drug exposure directly translates to superior efficacy. No consistent overall survival association exists. The relationships of adverse events remain unclear due to inconsistent study outcomes. These findings highlight the need for personalized dosing strategies through further research.

The aim of the present study was to investigate the prevalence of oral manifestations among patients undergoing chemotherapy.

Background/Objectives: P-glycoprotein (P-gp, ABCB1/MDR1) is a key ATP-binding cassette transporter involved in multidrug resistance in cancer, limiting intracellular accumulation of various chemotherapeutic (CT) agents. Several antidepressants (ADs) have been shown to modulate P-gp function. This dual pharmacological profile raises the possibility of repurposing ADs as chemosensitizers to enhance anticancer drug efficacy. The objective of this review was to summarize the available evidence on the combined use of ADs and chemotherapeutics to overcome P-gp-mediated resistance. Methods: A systematic search was performed in PubMed, Scopus, and PsycInfo/PsycArticles databases using a comprehensive search string combining terms for P-gp, ADs, chemotherapy, and drug resistance. Inclusion criteria were preclinical or clinical studies investigating the effect of ADs in combination with chemotherapeutics on P-gp-mediated resistance in cancer models. Eleven relevant studies were identified and qualitatively analyzed. Results: Across diverse cancer models, including colon, breast, and multidrug-resistant cell lines, several ADs significantly enhanced the cytotoxicity of many chemotherapeutic agents. The proposed mechanisms involved downregulation of P-gp expression, inhibition of efflux activity, and increased intracellular drug accumulation. Conclusions: The combination of ADs with CT agents shows promising potential in overcoming P-gp-mediated multidrug resistance, enhancing antitumor efficacy in preclinical models. Further translational and clinical research is needed to validate these findings, optimize dosing strategies, and assess the risk-benefit profile in cancer patients, particularly those with comorbid depressive disorders.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have significantly improved survival outcomes in small cell lung cancer (SCLC). However, ICIs can cause treatment-related adverse events (TRAEs), particularly immune-related adverse events (irAEs), which may compromise treatment efficacy and patient quality of life. Most ICI safety data is derived from clinical trials, which may not reflect real-world populations. This systematic review evaluated the real-world safety of ICIs compared to other therapies in SCLC. METHODS: A systematic search of MEDLINE, Embase, Scopus, CINAHL was conducted from inception to July 21, 2025. Eligible studies were observational cohort studies reporting safety outcomes for ICIs versus other cancer therapies (e.g., chemotherapy, targeted therapy) in SCLC. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative synthesis was conducted to summarise key findings. RESULTS: Twenty retrospective cohort studies were included, all using electronic health record data. Cohort sizes ranged from 14 to 188 patients. Nineteen studies were rated as poor quality due to inadequate adjustment for confounding variables. Across studies, TRAE incidence was comparable between ICI plus chemotherapy combination and chemotherapy alone. Similarly, TRAE and irAE rates were consistent across different ICI plus chemotherapy regimens. Evidence comparing ICIs to targeted therapy was limited. CONCLUSION: Real-world evidence suggests that adding ICIs to chemotherapy does not substantially increase toxicity in patients with SCLC, and safety profiles are generally consistent across ICI regimens. However, findings are constrained by small sample sizes and poor methodological quality. High-quality, large-scale observational studies are needed to validate these results and better inform clinical decision-making.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with other agents have emerged as the standard first-line treatment for metastatic hepatocellular carcinoma (HCC), replacing tyrosine kinase inhibitors (TKIs). However, the comparative efficacy and safety of different ICI-based combinations remains unclear. OBJECTIVE: To evaluate the efficacy and safety of ICI-based combinations versus TKIs across different regimens through a systematic review and network meta-analysis (NMA) of phase III randomized controlled trials (RCTs). METHODS: A comprehensive literature search was conducted across major databases and conference proceedings between 2019 and 2024. Eligible studies included phase III RCTs that evaluated ICI combinations in the first-line setting for metastatic HCC. Pairwise meta-analysis and Bayesian NMA were performed to assess overall survival (OS), progression-free survival (PFS), overall response rate (ORR), treatment-related adverse events (TRAEs), grade 3–4 TRAEs, and therapy discontinuation owing to toxicity. RESULTS: Six RCTs comprising 3937 patients were included in the study. Compared with TKIs, ICI-based combinations improved OS (OR, 0.72; 95% CI: 0.58–0.91) and ORR (OR: 3.13; 95% CI: 2.07–4.47), without significantly increasing TRAEs. No significant benefit was observed in PFS (OR, 0.81; 95% CI: 0.56–1.19). The NMA rankings suggested camrelizumab plus rivaroceranib (CAM+ RIVO), nivolumab plus ipilimumab (NIVO + IPI), and durvalumab plus remelimumab (DURVA + TREME) as the most effective regimens for OS, PFS, and ORR, respectively. DURVA + TREME appeared to have the best safety profile, and CAM + RIVO was associated with higher rates of treatment discontinuation due to toxicity. CONCLUSION: ICI-based combinations are more effective than TKIs in improving the OS and ORR in patients with metastatic HCC, with an acceptable safety profile. CAM + RIVO, NIVO + IPI, and DURVA + TREME have emerged as promising first-line options, although direct comparisons in future trials are warranted to confirm these findings.

Antineoplastic agents are toxic compounds, generally used in the treatment of cancers, which are recognized as carrying a cancer development risk. In this systematic review and meta-analysis of human biomonitoring studies, we have assessed the effects of exposure to antineoplastic drugs on levels of DNA strand breaks in leukocytes, measured by the comet assay. Focusing on the application of the comet assay in human biomonitoring of occupational exposure to antineoplastic agents, we have analyzed 458 original research studies which used this assay, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA-ScR). The systematic review led to 23 studies, of which 20 studies met the criteria for inclusion in the meta-analysis. Using standardized mean difference and 95% confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to antineoplastic drugs (1.26, 95% CI: 0.78, 1.73). Results originate mainly from studies on healthcare workers, with only one study in an industrial setting. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.77, 95% CI: 1.00, 2.55) than studies from high-income countries (0.49, 95% CI: 0.09, 0.90). This difference between middle- and high-income countries may be attributable in part to differences in exposure levels or exposure assessment. Additionally, sensitivity analysis indicates that studies with moderate/high risk of comet assay measurement bias have higher effect size (2.07, 95% CI: 0.82, 3.31) than studies with low risk of bias (0.73, 95% CI: 0.34, 1.13); and that studies with high risk of exposure misclassification have higher effect size (1.47, 95% CI: 0.89, 2.06) than studies with low/moderate risk (0.13, 955 CI: -0.08, 0.33). Most studies have low/moderate risk of bias related to the comet assay procedure (15 out of 20 studies), absence of reporting the use of assay controls (1 out of 20 studies), blinded analysis of samples (7 out 20 studies); exposure assessment (16 out of 20 studies). In conclusion, this systematic review and meta-analysis shows that exposure to antineoplastic drugs is associated with increased levels of DNA strand breaks in human leukocytes.

BACKGROUND: Lung cancer remains the foremost cause of cancer-related mortality worldwide. With the expanding use of PD-1/PD-L1 inhibitors in its treatment, a comprehensive understanding of their safety profiles and economic implications is essential to guide clinical decision-making. OBJECTIVE: This study evaluates the safety and economics of PD-1/PD-L1 inhibitors in NSCLC. Our findings indicate that they are a cost-effective option with a favorable benefit-risk profile, offering practical guidance for immunotherapy decisions. METHODS: We have conducted a comprehensive literature search for randomized controlled trials (RCTs) evaluating PD-1/PD-L1 inhibitors in PubMed, Web of Science, and the Cochrane Library up to August 2025. Eligible studies were limited to English-language RCTs relevant to network meta-analysis (NMA). This systematic review and NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction was carried out independently by two investigators. The data were then synthesized using a Bayesian random-effects model for NMA. The primary outcome was the incidence of immune-related adverse events, which was analyzed and compared across different PD-1/PD-L1 inhibitor regimens. RESULTS: A total of 60 eligible articles were involved, covering 13 treatments and 23,992participants. The safety evaluation revealed significant differences in toxicity profiles among PD-1/PD-L1 inhibitors, highlighting treatment-specific adverse effect patterns. Based on disability-adjusted life years (DALYs), the pharmacoeconomic analysis identified pembrolizumab as a dominant therapeutic strategy. CONCLUSIONS: Among the evaluated regimens, nivolumab plus ipilimumab was associated with the broadest toxicity spectrum. Sintilimab demonstrated a more favorable safety profile than other PD-1/PD-L1 inhibitors and ranked highest in the safety assessment.Our pharmacoeconomic analysis identified pembrolizumab as the most cost-effective option across treatment lines for NSCLC. The protocol was registered in advance in PROSPERO online platform as CRD42023442502.

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 80-85% of cases. Most patients are diagnosed at advanced stages, where curative treatment is no longer feasible. Current treatment options, including surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy, often result in limited efficacy and significant side effects. Chemotherapy regimens, in particular, have reached a therapeutic plateau, necessitating the development of more effective and tolerable therapeutic approaches.

Nasopharyngeal carcinoma (NPC) has a poor prognosis, largely due to immune escape. The programmed cell death protein 1 (PD-1) receptor and its ligand, PD-L1, play critical roles in this immune evasion. Consequently, blocking the PD-1/PD-L1 pathway with immune checkpoint inhibitors has become an established therapeutic strategy.

Esophageal cancer exhibits peak incidence in Asia and Africa, representing the sixth most common malignancy and seventh leading cause of global cancer mortality. Esophageal squamous cell carcinoma (ESCC) constitutes 90% of esophageal cancer cases. The European Medicines Agency approved programmed death 1 (PD-1) inhibitors plus chemotherapy as a first-line treatment for high PD-1-expressing ESCC.