Tankyrase as a Novel Molecular Target in Cancer and Fibrotic Diseases.

Abstract

Tankyrases belong to a group of enzymes called poly ADP ribosyl polymerases (PARPs). With the advent of a new class of small molecule inhibitors of PARP for clinical use like OLAPARIB; that gained accelerated approval by the USFDA in treating ovarian and breast cancers, the horizons of the PARPs as a novel target in various disease conditions has risen. Tankyrases (PARP 5) are yet another class of PARPs that perform poly ADP ribosylation on different substrate proteins aiding in progression of many diseases like cancer, fibrosis, diabetes and neurological disorders even. Few of the substrates of Tankyrases are Telomeric Repeat binding Factor protein (TRF1), Axis Inhibitory protein (AXIN 1&2), Insulin Responsive Amino Peptidase (IRAP), Nuclear Mitotic Apparatus protein (NuMa), that become aberrantly active due to the apparent overexpression of the enzyme during hyper proliferative disease conditions like cancer, fibrosis and metabolic disorders like diabetes. Tankyrases intervene in many physiological processes like cell growth and survival by affecting the Wnt signaling pathways. On the other hand, these functions are overdone during cancer and fibrosis especially. The development of novel therapies for cancer is a never ending process pertaining to several issues associated with current anticancer drugs like development of drug resistance and toxicity. A fibrotic disease like lung fibrosis is a debilitating condition with limited treatment options and survival rate. Tankyrase inhibition by specific small molecule inhibitors can therefore become a good combinatorial or single treatment strategy in treating hyper proliferative diseases and diabetes. In light of all these concerns, this article aims to brief the role of Tankyrase and the relevance of its inhibition to overcome the hurdles faced by current treatment regimens.