New research indicates that TNF-receptor associated protein-1 (TRAP-1) may prevent cancer cell death.
Prostate cancer most commonly develops in men over the age of 50 and is slow-growing; however, it may metastasize to other organs, particular to the bones and lymph nodes.
Prostate cancer cells are often resistant to cell death.
Thus, researchers led by Dr. Dario C. Altieri of the University of Massachusetts Medical School, explored the role of TRAP-1, a protein thought to regulate cell death, in prostate cancer survival.
TRAP-1 was highly expressed in both high-grade human prostate cancer lesions and mouse models of prostate cancer, but not in benign or normal prostate tissue.
In addition, TRAP-1 over expression in non-cancer prostate cells inhibited cell death, whereas TRAP-1-deficient prostate cancer cells had enhanced levels of cell death.
Moreover, treatment with Gamitrinib, which inhibits TRAP-1, resulted in prostate cancer cell death, but not death of non-cancerous prostate cells.
Therefore, the researchers observed that targeting TRAP-1 via Gamitrinib treatment could be a viable therapeutic strategy for patients with advanced prostate cancer.
"TRAP-1 [is] a novel marker of localized and metastatic prostate cancer, but not normal glands, required for prostate cancer cell viability, in vivo. Taken together with the preliminary safety of Gamitrinibs in preclinical studies, these data suggest that targeting mitochondrial TRAP-1 may provide a novel therapeutic approach for patients with advanced and metastatic prostate cancer" A similar approach may be also suitable for other types of cancer, as TRAP-1 is broadly expressed in disparate human malignancies. In future studies, Dr. Altieri and colleagues plan to "further dissect the biology of TRAP-1 cytoprotection in cancer cells, and test whether disabling its function may overcome drug resistance, the most common reason of treatment failure and dismal outcome in patients with advanced prostate cancer," said Leav et al.
The study appears in the latest issue of the American Journal of Pathology.