nilotinib + doxorubicin

Nilotinib + doxorubicin is a combination therapy investigated for the neoadjuvant treatment of resectable retroperitoneal sarcomas, including liposarcoma and leiomyosarcoma, as well as high-grade chondrosarcoma. Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) that targets BCR-ABL, c-KIT, and PDGFR. Beyond its direct kinase inhibition, nilotinib acts as an inhibitor of P-glycoprotein (ABCB1), a multidrug resistance protein that often pumps chemotherapy agents like doxorubicin out of cancer cells. Doxorubicin (adriamycin) is a cytotoxic anthracycline that works by intercalating into DNA and inhibiting topoisomerase II, leading to double-strand breaks and apoptosis. The combination is designed to leverage nilotinib's ability to sensitize sarcoma cells to doxorubicin by inhibiting efflux pumps and potentially blocking growth factor signaling pathways. This specific regimen was evaluated in the GEIS-27 trial led by Dr. Javier Martín Broto and the Spanish Sarcoma Group (GEIS).

Brand names

TasignaAdriamycin

Other names

nilotinib + adriamycin