Acquired sunitinib resistance poses a major clinical challenge in clear cell renal cell carcinoma (ccRCC). We integrated cross-model transcriptomic analysis of resistant cell lines, multi-algorithm protein-protein interaction screening, longitudinal patient-derived xenograft (PDX) profiling, and clinical ccRCC tissue analysis. This framework prioritized a 14-gene interferon-stimulated module that was concordantly upregulated in A498 and 786-O resistant sublines and showed coordinated activation during the therapeutic escape phase in a PDX model. Pathway enrichment linked the module to type I/II interferon signaling and antiviral defense. In cross-sectional clinical ccRCC tissues without annotated sunitinib treatment histories, the module was also more highly expressed than in normal kidney and displayed altered co-expression patterns. This finding supports disease-associated activation but does not establish resistance specificity. Collectively, the data identify a tumor-cell-intrinsic component associated with acquired sunitinib resistance and temporally aligned with therapeutic escape. Functional perturbation and longitudinal patient studies are required to determine causality and predictive value.

Malignant tumors remain a leading cause of global mortality, and the development of chemoresistance represents a major obstacle to effective cancer treatment. Long non-coding RNAs (lncRNAs) are important regulators of tumor progression and therapeutic response. Cancer susceptibility candidate 2 (CASC2) is an lncRNA that is generally downregulated in malignant tumors and has been implicated in the regulation of chemoresistance. CASC2 influences therapeutic responsiveness through multiple mechanisms, including modulation of apoptosis and oncogenic signaling pathways, competitive binding to specific miRNAs, regulation of protein stability and RNA-protein interactions, and epigenetic gene regulation. Notably, its effects may vary according to tumor type and treatment context. This review systematically summarizes the regulatory roles and molecular mechanisms of CASC2 in tumor chemoresistance and discusses its potential clinical and therapeutic implications.

The benefit of adding programmed cell death protein 1 (PD-1) blockade to hepatic arterial infusion chemotherapy (HAIC) plus lenvatinib for unresectable hepatocellular carcinoma remains uncertain. This single-center retrospective cohort study included 373 patients. After propensity score matching, 107 patients treated with HAIC plus lenvatinib alone and 107 patients treated with a PD-1 inhibitor were analyzed. Outcomes included overall survival (OS), progression-free survival (PFS), tumor response, and adverse events. PD-1 therapy was associated with longer OS (median, 22.5 vs 13.8 months; adjusted hazard ratio, 0.61; 95% CI, 0.40-0.94; p = 0.025) and a higher objective response rate (52.3% vs 40.2%, p = 0.075). The adjusted PFS difference was significant (hazard ratio, 0.67; 95% CI, 0.48-0.92; p = 0.015). No statistically significant differences in survival were detected among sintilimab, camrelizumab, and pembrolizumab. Grade 3-4 adverse events were comparable. Adding PD-1 blockade was associated with longer OS without substantially increasing severe toxicity.

Intensive care unit (ICU) patients are at high risk for colonization with multidrug-resistant organisms (MDROs) and Candida species, which frequently precedes invasive infections. However, the longitudinal acquisition dynamics and time-dependent relationship between colonization and subsequent clinical infection remain incompletely defined. We conducted a prospective longitudinal cohort study including 290 adult ICU patients. Patients were followed throughout their ICU stay with serial weekly surveillance cultures. Active surveillance screened for four major organism groups: carbapenem-resistant or extended-spectrum β-lactamase (CR/ESBL)-producing Gram-negative bacteria (GNB), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Candida species. Prior colonization was modeled as a time-varying exposure. The association between colonization and subsequent infection was evaluated using time-dependent Cox proportional hazards models with a one-week lag period. The mean ICU length of stay was 23.4 ± 19.1 days. Overall cumulative colonization rates were 37.6% (n = 109) for CR/ESBL-producing GNB, 25.5% (n = 74) for VRE, 16.6% (n = 48) for Candida species, and 16.2% (n = 47) for MRSA. Although VRE was the second most common colonizer, zero clinical VRE infection events occurred during ICU follow-up, precluding its inclusion in multivariable infection risk modeling. In time-dependent Cox regression analyses, prior colonization significantly increased the hazard of subsequent clinical infection across all evaluable pathogen groups: CR/ESBL-producing GNB (adjusted hazard ratio [aHR] 2.89, 95% confidence interval [CI] 1.82-4.59, P < 0.001), MRSA (aHR 4.02, 95% CI 1.37-11.79, P = 0.011), and Candida species (aHR 3.99, 95% CI 1.78-8.92, P = 0.001). Prolonged ICU stay and pre-acquisition broad-spectrum antimicrobial exposure were consistent independent predictors of colonization acquisition. Prolonged ICU stay is associated with progressive cumulative acquisition of MDRO and Candida colonization, which was independently associated with an increased hazard of subsequent infection. Although VRE colonization was relatively frequent, no transition to clinical infection was observed during ICU follow-up. Given the observational design of our study, this finding should be interpreted cautiously as a reflection of sample size constraints rather than a measure of infection-control efficacy.

Breast cancer is the most common malignancy in women, and pharmacotherapy is the cornerstone of multidisciplinary care. However, drug resistance severely impairs therapeutic efficacy and patient prognosis. Circular RNAs (circRNAs) have become a key focus in breast cancer chemoresistance due to their high stability and specific expression profiles. This review classifies circRNA functions according to breast cancer molecular subtypes, elucidating their regulatory mechanisms underlying drug resistance via RNA-RNA crosstalk, RNA-protein binding, and translational regulation. We systematically summarize the core signaling cascades through which circRNAs modulate downstream biological events, including drug efflux and DNA damage repair, to drive resistance, and highlight the vital function of exosomal circRNAs in propagating systemic drug resistance. We integrate existing research evidence into a comprehensive landscape of subtype-specific circRNA regulatory networks in breast cancer drug resistance.

Cancer treatment is difficult, there are many issues regarding cancer treatment because Protein Kinase Inhibitors (PKIs) are unable to control tumors that are resistant to them. Resistance to drugs starts with changes in genetic code and continues with fresh changes, routes and alterations in the tumour. When treating cancer with imatinib or osimertinib, PKIs can correct faulty signals, yet patients generally become resistant swiftly and this resistance can include unpleasant side effects. Reviewing Epidermal Growth Factor Receptor (EGFR) T790M and BCR::ABL1 T315I mutations reveals that the important interactions and binding sites are removed or obstructed with the drug. This is how researchers design second- and third-generation drug inhibitors. In addition, the use of single-cell sequencing, CRISPR screens and liquid biopsies helps researchers and doctors to accurately fight resistance in cancer patients. For cancer treatments to succeed, systems to reduce drug costs and make them available, fresh ideas, global experts and equitable healthcare laws should be implemented.

This multicenter retrospective study evaluated first-line treatment patterns, maintenance therapy outcomes, and prognostic factors in 171 newly diagnosed marginal zone lymphoma (MZL) patients treated across multiple centers in Fujian Province, China (2019-2024). The MALT subtype predominated (79.0%), with the gastrointestinal tract and lung being the most common primary sites. The first-line overall response rate was 91.1%, with 67.3% of patients achieving complete remission. Five-year progression-free survival (PFS) and overall survival (OS) were 82.6% and 94.7%, respectively. Maintenance therapy, received by 66.1% of patients, was associated with superior 5-year OS (100% vs. 87.5%, P=0.0104). Multivariate analysis identified Ki-67 >20% (HR=3.208, P=0.024) and high tumor burden (HR=4.670, P=0.003) as independent negative predictors for PFS, while high tumor burden (HR=4.493, P=0.004) and B symptoms (HR=3.324, P=0.030) predicted worse OS. Chinese MZL patients demonstrated favorable outcomes, and maintenance therapy conferred a significant OS benefit. Ki-67, tumor burden, and B symptoms serve as practical prognostic indicators to inform risk stratification and personalized treatment planning.

Hepatocellular carcinoma (HCC) frequently develops resistance to tyrosine kinase inhibitors (TKIs) like sorafenib - the first FDA-approved systemic therapy for advanced HCC - yet early resistance mechanisms remain unclear. Short-term sorafenib exposure in sensitive HCC cells induces global m[6]A reduction and rapid upregulation of the demethylase ALKBH5. High ALKBH5 expression correlates with poor prognosis in sorafenib-treated HCC patients. Functionally, ALKBH5 overexpression enhances sorafenib resistance, clonogenicity and epithelial-mesenchymal transition (EMT) by stabilizing β-catenin and activating Wnt/β-catenin signalling. Thus, ALKBH5 is a key early driver of sorafenib resistance via the Wnt/β-catenin pathway and may serve as both a prognostic biomarker and therapeutic target in HCC.

Immune checkpoint inhibitor (ICI) resistance remains a major challenge in esophageal squamous cell carcinoma (ESCC). This study investigates the role of glutaminase (GLS) in modulating the tumor immune microenvironment and its impact on immunotherapy response. Bioinformatic analysis of TCGA data revealed an inverse correlation between GLS expression and CD8[+] T cell infiltration. In ESCC clinical specimens, high GLS expression correlated with elevated CXCL8 levels and reduced CD8[+] T cell infiltration. Mechanistically, our data support an association between GLS expression and increased CXCL8 transcription, accompanied, at least in part, by HAT-dependent enhancement of H3K27 acetylation at the CXCL8 promoter region. In advanced ESCC patients receiving immunochemotherapy, high tumoral GLS expression was associated with significantly shorter progression-free survival. In vitro and in vivo functional studies showed that GLS knockdown in ESCC cells was associated with enhanced T-cell effector cytokine secretion, increased tumor infiltration of CD8[+] T cells, and greater tumor suppression when combined with anti-PD-1 therapy in a humanized mouse model. Importantly, exogenous CXCL8 supplementation partially reversed the increased Granzyme B and IFNγ secretion induced by GLS knockdown in the co-culture system, supporting a functional role for CXCL8 in GLS-associated immune suppression. These results support a model in which GLS contributes to an immunosuppressive microenvironment in ESCC, at least in part through epigenetic upregulation of CXCL8. These findings support further investigation of GLS targeting as a potential strategy to improve immunotherapy response in ESCC.

This Systematic review provides a comprehensive framework for understanding current therapeutic options and future directions in prostate cancer treatment. It highlights ongoing efforts, focusing on AR signaling inhibitors (ARSi) and novel molecularly targeted therapies. Using PRISMA-ScR guidelines, we conducted a comprehensive literature search across significant databases (MEDLINE/PubMed, Embase, and Cochrane Library). Next-generation ARSi (enzalutamide, apalutamide, darolutamide) have demonstrated significant survival benefits across various stages of prostate cancer, as evidenced by pivotal trials (PROSPER, SPARTAN, ARAMIS). The emergence of promising therapeutic approaches for biomarker-defined patient subgroups, including PARP inhibitors (PROfound, TRITON2), radioligand therapy (VISION, TheraP), and immunotherapy (KEYNOTE-199, CheckMate 650), is increasingly clinically relevant. While significant advances have been made in AR-targeted therapies, emerging molecular-targeted approaches are reshaping the treatment landscape. Our data provide a comprehensive framework for understanding current therapeutic options and future directions in prostate cancer treatment, engaging the audience and making them feel part of the solution.

Overall survival (OS) has improved in unresectable/metastatic pancreatic adenocarcinoma (mPDAC) patients. However, it is unclear who should be offered further treatment, and how to assess the response in unmeasurable disease. The study aims to evaluate the role of 6-month progression-free survival (PFS) and the corresponding tumor growth rate after first-line chemotherapy (G6m). After identifying 15 randomized trials (19 cohorts, 4,725 patients), 6-month PFS were extracted from curves and expressed as G6m. Median G6m was higher after polychemotherapy and was significantly associated with OS (β = 0.168; p-value <0.001). The number of drugs and female sex correlated with a slower tumor growth rate. Since it was calculated directly from PFS in this study, it is not surprising that G6m exhibits a similar behavior. However, it can be derived by imaging or other markers, therefore representing a variable distinct from PFS, and as such warrants further evaluation in future studies.

Interpatient variability in chemotherapy response and toxicity remains a major challenge in oncology. Pharmacogenomics (PGx) is an approach to address this challenge by combining somatic alterations that affect tumour sensitivity with germline variants that affect drug metabolism, transport and toxicity. This review provides a critical evaluation of clinically validated PGx biomarkers for chemotherapeutics and targeted therapy with a focus on translational relevance and strength of evidence. High-impact germline markers such as DPYD, TPMT, NUDT15 and UGT1A1 are highlighted as key determinants of genotype-guided dosing for improving safety without compromising efficacy. Somatic biomarkers such as EGFR, RAS, BRAF, and HER2 remain central to treatment selection, while resistance underscores the need for ongoing molecular assessment. A tiered implementation framework, barriers to progress, and future directions involving polygenic models, multi-omics, and artificial intelligence (AI) are discussed to advance safe, effective, and personalized chemotherapy.

The aim of this study is to evaluate the efficacy and safety of TROP2 antibody-drug conjugate (ADC) -based regimen in the treatment of HER2-negative advanced breast cancer and non-small cell lung cancer (NSCLC) in real environment to fill the evidence gap. A total of 130 patients (median age 55 years) were included in the study. The median progression-free survival (mPFS) of 75 NSCLC patients was 10.0 (95%CI: 5.130-14.870) months. The mPFS of 21 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) patients was 6.0 (95%CI: 4.217-7.783) months. The mPFS of 34 triple-negative breast cancer (TNBC) patients was 5.0 (95%CI: 2.845-7.158) months. In patients with TNBC, mPFS was significantly shorter with sacituzumab govitecan monotherapy than with sacituzumab tirumotecan monotherapy (2.0 months vs 6.0 months, p = 0.036). In patients with NSCLC, mPFS was significantly longer in those receiving sacituzumab tirumotecan monotherapy as first-and second-line therapy than in those receiving third-line or more therapy (17.0 vs 7.0 months, p = 0.0026). The incidence of adverse events was 63.8% (≥ grade 3 accounted for 38.5%), mainly anemia, leukopenia, etc. The existing evidence suggests that TROP2 ADC has certain anti-tumor activity in advanced HER2-negative breast cancer and NSCLC, which provides limited support for its exploration in first-line combination and early treatment. However, the actual improvement effect on survival endpoints is still unclear and needs to be verified by large prospective phase III studies. At the same time, long-term safety signals and acquired drug resistance also need continuous attention.

This study aimed to evaluate the safety and efficacy of PD-1/PD-L1 ICI plus chemotherapy versus chemotherapy alone in ES-SCLC, following PRISMA guidelines.23 studies(10RCTs,13RWSs) with 6364 patients were enrolled,with OS,PFS,ORR and grade 3-4 AEs as primary endpoints. Pooled analyses demonstrated that ICI + chemotherapy (CT) significantly improved OS (HR = 0.68) and PFS (HR = 0.60), and ORR (RR = 1.13). Subgroup analyses confirmed consistent OS/PFS benefits in both RCT and RWS cohorts. Both PD-1 and PD-L1 inhibitors improved survival; PD-1 inhibitors yielded greater PFS benefit(HR=0.49) and significant ORR improvement, while PD-L1 inhibitors showed no significant ORR elevation. The combination slightly increased overall AEs with no difference in severe events, with manageable safety.This meta-analysis supports chemoimmunotherapy as first-line treatment for ES-SCLC.