P38 MAPK PATHWAY PREDICTS ENDOCRINE-RESISTANT GROWTH OF HUMAN BREAST CANCER AND PROVIDES A NOVEL DIAGNOSTIC AND TREATMENT TARGET

摘要

Acquired and de novo endocrine resistance are major clinical problems in the management of breast cancer patients. Though the antiestrogen tamoxifen prolongs disease-free and overall survival in the adjuvant setting, and induces remissions in over half of the patients with estrogen receptor positive metastatic disease, all patients eventually acquire tamoxifen resistance. Furthermore, many of the resistant tumors actually appear to be stimulated by tamoxifen just as they are by estrogens. The present invention provides methods of predicting endocrine resistance comprising detecting the biological activity and/or expression of p38 MAPK and/or AIB1. The invention further provides methods of reducing, reversing, or preventing endocrine resistance comprising contacting a breast or prostate tumor with a p38 MAPK pathway inhibitor.