Published online May 26, 2017. doi: 10.4331/wjbc.v8.i2.102
Peer-review started: December 6, 2016
First decision: January 16, 2017
Revised: February 22, 2017
Accepted: March 12, 2017
Article in press: March 13, 2017
Published online: May 26, 2017
Processing time: 163 Days and 21.9 Hours
Obesity and cancer are two interrelated conditions of high epidemiological need, with studies showing that obesity is responsible for nearly 25% of the relative contribution to cancer incidence. Given the connection between these conditions, a drug that can operate on both obesity and cancer is highly desirable. Such a drug is accomplishable through the development of potent anti-angiogenesis agents due to the shared underlying role of angiogenesis in the development of both diseases. Prior research has demonstrated a key role of type-2 methionine aminopeptidase (MetAP2) for angiogenesis, which has led to the development of numerous of novel inhibitors. Several irreversible MetAP2 inhibitors have entered clinical trials without great success. Though this lack of success could be attributed to off-target adverse effects, the underlying causes remain unclear. More promising reversible inhibitors have been recently developed with excellent pre-clinical results. However, due to insufficient knowledge of the biological functions of N-terminal protein processing, it is hard to predict whether these novel inhibitors would successfully pass clinical trials and thereby benefit cancer and obesity patients. Significantly more efforts are needed to advance our understanding of the regulation of methionine aminopeptidases and the processes by which they govern the function of proteins.
Core tip: There were approximately 14 million new cancer cases worldwide each year and more than half of the population in the developed countries are overweight or obese. Obesity is responsible for nearly 25% of the relative contribution to cancer incidence, which ranks second only to tobacco use. It would be, therefore, highly desirable to have drugs that work for both cancer and obesity. In this article, the biological function of a common therapeutic target, methionine aminopeptidase-2, and the status of some of its inhibitors in pre-clinical and clinical trials for cancer and/or obesity were discussed.