Mechanistic insights into the oncogenic partnership of hADA3 and HPVE6 - paving ways for improved cervical cancer therapy

Abstract

High risk Human Papillomavirus (HPV) is considered the primary causative agent of cervical cancer, a devastating malady with significant morbidity. In India, cervical cancer is one of the major reasons of cancer mortality among women. Poor treatment outcomes of this disease is a matter of grave concern and hence demands aggressive research efforts towards discovery of more effective therapies. Understanding the intricacies of HPV oncogenesis at the molecular level can facilitate the discovery of promising anti-viral drugs. Our research aims at catering to the need of the time by revealing some of the key molecular mechanisms that contributes to HPV oncogenesis that can be utilized to discover promising anti-cancer molecules. We delineated the oncogenic connections between hADA3 and HPVE6 and illustrated its critical role in cellular transformation. Our work also shows how HPV oncoproteins exploits the cellular SUMO machinery to downregulate hADA3 to induce malignancy. This intrigued us to identify the hot spots of hADA3-E6 interaction and design therapeutic peptides against HPV induced cervical cancer. Present review is an attempt to outline our research on novel mechanisms of HPV pathogenesis and its implication on development of improved cervical cancer therapies.