Inhibiting CD36 to overcome resistance to Tykerb in HER2-positive breast cancer

INDICATION: Breast cancer

Inhibiting CD36, a fatty acid transporter, could treat HER2-positive breast cancer and sensitize tumors resistant to Tykerb lapatinib. In patients with HER2-positive breast cancer, CD36 protein levels were higher in grade III tumors than in grade II tumors; and high tumor levels of CD36 were associated with poor overall survival. Gene expression analysis revealed CD36 as one of the most upregulated genes in Tykerb-resistant vs. sensitive human HER2-positive breast cancer cell lines. An siRNA against CD36 induced apoptosis in the resistant cells and a CD36 inhibitor tool compound sensitized the cells to Tyverb. In mice with Tykerb-resistant breast cancer, mammary-specific CD36 knockout decreased tumor growth and extended median survival; and a mAb against CD36 sensitized tumors to the EGFR and HER2 inhibitor...