Taking aim with IAP antagonists at triple-negative breast cancer: a moving target no more?

Abstract

Triple-negative breast cancer (TN-BC) is a malignancy with the worst prognosis for all four corresponding stages compared with other receptor-positive BCs 1. TN-BC account for 10-20% of all BCs, with BC affecting one in nine women over their lifespan. TN-BC is defined by immunohistochemistry as lacking the estrogen receptor (ER-negative), the progesterone receptor that is normally induced by functional estrogen receptor (PR-negative) and lacking the human epidermal growth factor 2 (Her2) receptor overexpression or amplification as well (Her2negative). Hence, TN-BC is nonresponsive to targeted BC therapies such as small-molecule endocrine therapies typified by anti-estrogens (ER antagonists) or aromatase inhibitors (that block conversion of endogenous androgens to estrogens), and alternatively to biologics that target the Her2 plasma membrane receptor. These targeted therapies have become mainstays in BC treatment and adjuvant therapy resulting in improved survival for those receptor-positive BC patients. Traditional cytotoxic chemotherapy, consisting of taxanes and other agents, remains the only therapeutic option for metastatic TN-BC. The limited success with these drugs drives the need for new effective therapies for this "untargetable" BC.