VEGF-mTOR signaling links obesity and endometrial cancer

Over past few decades, the incidence of endometrial cancer (cancer of the uterine lining) continues to grow at a faster rate among all the gynecological cancer types. Out of several risk factors (genetic predisposition, family history, hormone replacement therapy, early menarche, and late menopause), lifestyle factors such as high-fat diet and overweight has a significant contribution towards this unfortunate trend. A recent statistic shows that more than half of endometrial cancers (57%) are due to obesity [1]. In addition, epidemiological evidence from both casecontrol and cohort studies show a linear rise in the risk of endometrial cancer with increasing BMI (body mass index). As the global obesity epidemic has shown no signs of abating, particularly in the western countries, it is speculated an endometrial cancer tsunami is coming! In case of obesity, the number of adipose progenitor cells increases, which synthesize surplus adipocytes. These hypertrophied adipocytes play a relevant role in endometrial cancer patients via several pathways such as insulin resistance, leptin resistance, secretion of adipokines, and in situ synthesis of estrogen [2]. Of note, insulin resistance has been observed in case of type 2 diabetes patients, as well as excess estrogen in women, also potentiates breast and ovarian cancer. Thus, at present, the biological mechanism clearly linking the strongest association of overweight or obesity to endometrial cancer is poorly understood. The molecular mechanisms by which cancer cell-adipocyte interactions promote malignant growth vary among tumor types. Although clinical and epidemiological data strongly support endometrial cancer risk in obese women, these concepts have yet to be characterized at the molecular Editorial