Our study demonstrates that CHD1L is markedly upregulated in prostate cancer and contributes to tumor progression. Pharmacological inhibition of CHD1L with the selective inhibitor OTI-611 significantly suppresses proliferation, migration, and invasion, while inducing apoptosis in vitro and in vivo. Mechanistically, these effects are mediated through activation of the FOXO3-PUMA axis, as FOXO3 suppression abrogates OTI-611-induced apoptosis. Moreover, OTI-611 exhibits strong synergy with docetaxel, enhancing apoptotic cell death and providing a potential strategy to improve therapeutic efficacy in prostate cancer.

In this study, we propose that an AREG-based signature comprising ACSM3, ACTG2, and DES effectively predicts prognosis and reflects immune microenvironment characteristics in PRAD. Through systematic analysis, we established a prognostic model utilizing these three AREGs, which demonstrates strong potential as a clinical predictor for PRAD patient outcomes.

Epithelial ovarian carcinoma, the deadliest gynecological malignancy, frequently develops treatment resistance through polyploid giant cancer cells (PGCCs) that typically emerge after carboplatin-paclitaxel chemotherapy. Our findings establish that the cytoplasmic SIRT1/β-catenin axis contributes to PGCC stemness, elucidating a novel mechanism underlying chemoresistance. Therefore, targeting cytoplasmic SIRT1 represents a promising therapeutic strategy to overcome PGCC-mediated resistance in this lethal carcinoma.

P2, N=25, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | Trial completion date: Jan 2027 --> Nov 2028 | Trial primary completion date: Jan 2027 --> Nov 2028

Functional studies reveal that HOMER3 overexpression enhances ECM stiffness, type I collagen deposition, and Aβ accumulation in the tumor stroma, leading to tumor growth and aggressiveness, while HOMER3 knockdown reduces ECM stiffness, disrupts collagen composition, and increases sensitivity to docetaxel. These findings establish HOMER3 as a pivotal regulator of OSCC malignancy and chemoresistance, providing novel insights into its role in orchestrating the tumor microenvironment and identifying it as a promising therapeutic target for OSCC.

Dato-DXd offers a promising treatment option for heavily pretreated patients with HR+/HER2- breast cancer and EGFR-mutant NSCLC, providing meaningful clinical benefit with a manageable safety profile. Optimal sequencing and positioning within the rapidly shifting ADC landscape requires further investigation.

GD-07 suppresses MYC expression, curbing glucose metabolism, and glycolysis while promoting p53 and proapoptotic markers in OC cells. In patient-derived OC organoids, GD-07 shows greater activity than carboplatin with promising clinical translatability.

This integrative bioinformatics approach prioritized functionally significant BCa-associated SNPs and identified promising candidates for biomarker development and drug repositioning. The nine high-scoring variants, including SLCO1B1 and ARHGEF38 emerge as biologically impactful genes, while MAPT's known drug interactions highlight its translational potential in repurposing existing anticancer agents.

Ten-year outcomes for TC and EC-T were similar and excellent; six cycles of TC is an effective option in HER2-negative eBC with pN0 or pN1 and intermediate-to-high-risk disease, according to gene expression analysis.

Mechanistically, SEL1L suppressed the expression of oncogenic Shh protein by promoting its ubiquitination-proteasomal degradation, thereby inhibiting EMT and improving cellular sensitivity to carboplatin in BRC cells via hedgehog signaling pathway. Our findings emphasize the tumor-suppressive function of endogenous SEL1L in BRC and demonstrate the crucial role of the SEL1L-Shh-Gli1 axis in controlling cancer cell progression, offering a promising foundation for the development of innovative therapeutics against BRC.

They received PPCT with paclitaxel/carboplatin or nab-paclitaxel/carboplatin, followed by esophagectomy 4-6 weeks after treatment. Although the short-term efficacy was not superior to that of neoadjuvant chemoradiotherapy, PPCT demonstrated acceptable safety and comparable one-year survival. We also revealed an association between the therapeutic response and the ability of anti-IL-6 blockade to enhance the efficacy of immunotherapy.

Correspondingly, a higher sensitivity to SRA737 was observed in a docetaxel-resistant CRPC cell line with elevated KDM5D, and silencing KDM5D caused resistance to this inhibitor. SIGNIFICANCE STATEMENT: This study demonstrated an important role of an epigenetic regulator KDM5D in regulating CHK1 inhibitor sensitivity via a p38/COX-2-mediated prosurvival pathway in certain castration- or drug-resistant PC cells. Our results indicate that PC cells expressing KDM5D may be more sensitive to targeted inhibition of CHK1 kinase, highlighting the potential predictive value of this gene for CHK1-targeted therapies in PC.