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. CD146neg 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 CD146pos CAFs enhances ER expression in ER+ breast cancer cells and sustains ER-dependent proliferation and sensitivity to tamoxifen. Co-cultures of CD146pos CAFs with tamoxifen-resistant breast cancer cells restores sensitivity to tamoxifen. Gene expression profiles of patient breast tumors with predominantly CD146neg 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.