Research Highlights

Pothana Saikumar, Ph.D.

Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with high metastatic and poor survival rates. TNBCs, which represent 15-20% of total breast cancer cases, are responsible for almost 50% of deaths due to breast cancer and are highly resistant to many therapeutic approaches. One of the prominent markers with poor prognosis and high metastasis is high transforming growth factor-beta (TGF-beta) signaling activity in breast cancer. Paradoxically, TGF-beta is a growth inhibitor of early tumors; however, during breast cancer progression tumor suppressive actions of TGF-beta are subverted to promote tumor growth and metastasis. Based on TGF-beta's ability to promote metastasis, TGF-beta inhibitors have been considered for breast cancer treatment. However, this approach carries the risk of developing new tumors because of TGF-beta's inability to suppress early tumor formation. Therefore, the knowledge of how TGF-beta becomes a tumor promoter from a tumor suppressor is essential to develop novel therapeutics for both cancer progression and cancer prevention. In this regard, we identified a novel gene, TMEPAIthat is overexpressed in several TNBCs, which plays a critical role in subverting the tumor suppressive effects of TGF-beta. Novel drugs that target TMEPAI would not only inhibit oncogenic functions of TGF-beta but also preserve or enhance the tumor suppressive actions of TGF-beta. We consider that these drugs will have both cancer therapeutic and cancer preventive capabilities.

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