melphalan + RAD51 inhibitor

melphalan + RAD51 inhibitor refers to an experimental combination regimen pairing the alkylating chemotherapy drug melphalan with a small‑molecule inhibitor of the homologous recombination repair protein RAD51, with the goal of overcoming DNA repair–mediated resistance and enhancing cytotoxicity in cancer cells. Melphalan is a nitrogen mustard that forms DNA interstrand cross‑links and other alkylation lesions, leading to replication arrest and apoptosis, while RAD51 is a central recombinase that mediates error‑free repair of DNA double-strand breaks and replication fork restart during homologous recombination.[3][5][8] Preclinical work in multiple myeloma and other tumor models shows that blocking RAD51 function (or closely related HR components) increases melphalan‑induced DNA damage markers such as γH2AX, reduces repair of cross‑link–associated breaks, and significantly sensitizes tumor cells to melphalan, supporting this combination as a synthetic lethality–style strategy to improve outcomes in melphalan‑treated malignancies.[1][4][8][13]