Mezquita, BetlemReyes, MajoriePons Vallès, Miquel2025-07-112025-07-112024-08-210753-3322https://hdl.handle.net/2445/222181Direct-acting antivirals ledipasvir (LDV) and daclatasvir (DCV) are widely used as part of combination therapies to treat Hepatitis C infections. Here we show that these compounds inhibit the proliferation, invasion, and colony formation of triple-negative MDA-MB-231 breast cancer cells, SRC-transduced SW620 colon cancer cells and SRC- transduced NIH3T3 fibroblasts. DCV also inhibits the expression of PDL-1, which is responsible for resistance to immunotherapy in breast cancer cells. The demonstrated low toxicity in many Hepatitis C patients suggests LDV and DCV could be used in combination therapies for cancer patients. At the molecular level, these direct-acting antivirals inhibit the phosphorylation of Akt and the ephrin type A receptor 2 (EPHA2) by destabilizing a Src-EPHA2 complex, although they do not affect the general kinase activity of Src. Thus, LDV and DCV could be effective drugs for Src-associated cancers without the inherent toxicity of classical Src inhibitors.9 p.application/pdfengcc-by-nc (c) Mezquita, Betlem et al., 2024http://creativecommons.org/licenses/by-nc/3.0/es/Proteïnes quinasesMedicaments antivíricsCèl·lules cancerosesProtein kinasesAntiviral agentsCancer cellsinfo:eu-repo/semantics/article7541902025-07-11info:eu-repo/semantics/openAccess39226729