Abstract: Elevated ETRB activity, BCL-2A1 activity and/or PARP-3 activity was detected in cancer cells, and determined to be associated with growth and proliferation of the cancer cells. Accordingly, methods are provided for treating cancer by reducing or inhibiting the ETRB activity, BCL-2A1 activity and/or PARP-3 activity. Also provided are methods of determining the responsiveness of cancer cells to treatment with inhibitors of ETRB activity, BCL-2A1 activity and/or PARP-3 activity. Further, decreased cell viability was observed to correlate with reduction in ETRB expression, and reduction in ETRB protein levels by siRNA led to an increase in cell death.

Abstract: Described herein are results which show that an endothelin receptor antagonist, BQ788, increases pigmentation and significantly reduces the viability of 7 human melanoma cell lines in culture. Moreover, it is described herein that administration of BQ788 significantly slows melanoma tumor growth in nude mice, including a complete growth arrest in half of the mice treated systemically. Thus, inhibitors of endothelin receptor activity are described herein as beneficial for the treatment of cancer.