Therapeutics: MicroRNA-196a (miR-196a); v-myc myelocytomatosis viral oncogene homolog (MYC; c-Myc); homeobox B7 (HOXB7)

Studies in patient samples, cell culture and mice suggest miR-196a or inhibition of MYC could help treat tamoxifen-resistant breast cancer. In tumors from estrogen receptor-positive breast cancer patients previously treated with tamoxifen, high levels of both MYC and HOXB7 were associated with poor survival. In tamoxifen-resistant human breast cancer cell lines, knockdown or pharmacological inhibition of MYC decreased HOXB7 levels and increased miR-196a levels and sensitivity to tamoxifen compared with no knockdown or vehicle. In the cell lines, vector-mediated overexpression of miR-196A decreased HOXB7 levels and estrogen receptor-mediated gene expression and increased tamoxifen sensitivity compared with empty vector. In xenograft mouse models of tamoxifen-resistant breast cancer, vector-mediated overexpression of miR-196a increased tumor responses to tamoxifen. Next steps could include combining miR-196a expression with MYC inhibition in the xenograft model.

Dicerna Pharmaceuticals Inc. has DCR-M1711, a Dicer substrate siRNA targeting MYC mRNA, in Phase I/II testing to treat liver cancer and Phase I testing to treat lymphoma, multiple myeloma (MM), liver cancer, neuroendocrine tumors and solid tumors...