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Lurbinectedin is a selective inhibitor of oncogenic transcription approved for the treatment of adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. Preclinical data provide evidence for lurbinectedin exerting its actions in a unique manner that involves oncogenic transcription inhibition, DNA damage, reshaping of the tumor microenvironment, and inducing anticancer immunity. Understanding the mechanism of action has facilitated the rational combination of lurbinectedin and anticancer therapies with complementary modes of action, in order to obtain synergistic effects that could potentially lead to improved efficacy. This review evaluates the mechanism of action for lurbinectedin and provides an overview of the therapeutic landscape with regards to lurbinectedin combination therapies for the treatment of small cell lung cancer based on data from preclinical and clinical studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134746 | PMC |
http://dx.doi.org/10.1158/1535-7163.MCT-24-0050 | DOI Listing |
Mutat Res Rev Mutat Res
September 2025
Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:
To maintain genomic stability, cells have evolved complex mechanisms collectively known as the DNA damage response (DDR), which includes DNA repair, cell cycle checkpoints, apoptosis, and gene expression regulation. Recent studies have revealed that long non-coding RNAs (lncRNAs) are pivotal regulators of the DDR. Beyond their established roles in recruiting repair proteins and modulating gene expression, emerging evidence highlights two particularly intriguing functions.
View Article and Find Full Text PDFJCO Precis Oncol
September 2025
Division of Hematology and Oncology, University of California Los Angeles, Los Angeles, CA.
Purpose: mutations are classically seen in non-small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with -mutated NSCLC. The real-world prevalence of -mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic mutations in ovarian cancer and describe a case of -mutated metastatic ovarian cancer with a durable response to osimertinib, an EGFR-directed targeted therapy.
View Article and Find Full Text PDFJ Leukoc Biol
September 2025
Laboratory of Immunobiology and Ionic Transport Regulation, Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Villa de San Sebastián, 28045 Colima, México.
Ion channels are integral membrane proteins which facilitate rapid transport of small ions into and out of the cell and between organelles and cytosol. Cytolytic lymphocytes including natural killer (NK) cells principally kill virus-infected and cancer cells by releasing cytolytic granules within the immunological synapse, formed between target and effector cells. This process strongly depends on Ca2+ signaling, which in human NK cells is controlled by the phospholipase C (PLCγ)/inositol-1,4,5-triphospate receptor (IP3R)/calcium release-activated calcium channel (CRAC) axis.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
Narrow electrochemical windows and high reactivity of aqueous solutions remain critical bottlenecks for the practical application of aqueous batteries. However, the mechanisms for tuning microscopic reactivity of HO molecules in aqueous electrolytes remain elusive. This study employs six ether molecules with distinct structures and solvation powers to regulate the microstructure of aqueous solutions.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2025
Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chronic diarrhea is a frequent gastrointestinal complication in both type 1 (T1D) and type 2 diabetes (T2D), although the underlying mechanisms differ: T1D is linked to autonomic neuropathy and disrupted transporter regulation, while T2D is often linked to medications and intestinal inflammation. Using streptozotocin-induced mouse models of T1D and T2D, we observed increased luminal fluid in the small intestine of both. Given the role of Na⁺/H⁺ exchanger 3 (NHE3) in fluid absorption and its loss in most diarrheal diseases, we examined NHE3 expression across intestinal segments.
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