TARGETING BREAST CANCER THERAPY BASED ON STROMAL SUBTYPES AND CD146 COMPOSITION

摘要

Methods for targeted breast cancer therapy in a subject based upon evaluating the stromal subtypes and CD146 composition in the adjacent tissue. ER+ breast cancers contain two CAF subtypes defined by CD146 expression. CD146^neg CAFs suppress ER expression in ER+ breast cancer cells, decrease tumor cell sensitivity to estrogen, switch ER proliferation dependency toward EGFR dependency and decrease tumor cell sensitivity to antiendocrine therapy. Conversely, the presence of CD146P^pos CAFs enhances ER expression in ER+ breast cancer cells and sustains ER-dependent proliferation and sensitivity to tamoxifen. Co-cultures of CD146^pos CAFs with tamoxifen-resistant breast cancer cells restores sensitivity to tamoxifen. Gene expression profiles of patient breast tumors with predominantly CD146^neg CAFs correlate with inferior clinical response to tamoxifen and worse patient outcomes. CAF composition contributes to treatment response and patient outcomes in ER+ breast cancer, and provide a target for drug development.