Phosphatidylinositol 3-kinase Signaling as a Therapeutic Target for Cervical Cancer

Jianghong      Wu; Chen      Chen; Kong-Nan      Zhao

doi:10.2174/1568009611313020004

Abstract

Cervical cancer is the second most frequent cause of female cancer mortality and remains a major health problem in women worldwide. Surgery, chemotherapy and radiotherapy alone or combined are the three treatments methods commonly used to treat this disease. However, a significant proportion of the cancer patients still experiences recurrence and eventually dies. Recently, the research advances in molecular profiling and genomics have revealed that the phosphatidylinositol 3-kinases (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in mediating multiple cellular functions including cell growth, proliferation, metabolism, survival and angiogenesis. Thus, targeting this signal pathway offers a promising perspective for cervical cancer therapy. In this article, we review the published data from both basic and clinical studies showing that the concurrent cervical cancer chemoradiotherapy dramatically improves the local control of this disease and overall survival by triggering tumor cell apoptotic pathways via the PI3K/AKT/mTOR signalings, proving that the PI3K/AKT/mTOR pathway is one of the most important targets for cervical cancer therapy. We also highlight that several phytochemicals strongly inhibit proliferation of the cervical cancer cells and induce apoptosis by targeting one or multiple molecules through the PI3K/AKT/mTOR pathway. While some of these phytochemicals have been used as therapeutic agents or chemoradiotherapy sensitizers, others are currently in clinical development to be the potential therapeutic agents for the advanced cervical cancer therapy.

Keywords: Cervical cancer, chemoradiotherapy, chemoradiosensitizers, growth factors, notch signalings, phytochemicals, PI3K/AKT/mTOR signalings, PI3K inhibitors.