Is viral E6 oncoprotein a viable target? A critical analysis in the context of cervical cancer

An understanding of the pathology of cervical cancer (CC) mediated by E6/E7 oncoproteins of high-risk human papillomavirus (HPV) was developed by late 80's. But if we look at the present scenario, not a single drug could be developed to inhibit these oncoproteins and in turn, be used specifically for the treatment of CC. The readers are advised not to presume the "viability of E6 protein" as mentioned in the title relates to just druggability of E6. The viability aspect will cover almost everything a researcher should know to develop E6 inhibitors until the preclinical stage. Herein, we have analysed the achievements and shortcomings of the scientific community in the last four decades in targeting HPV E6 against CC. Role of all HPV proteins has been briefly described for better perspective with a little detailed discussion of the role of E6. We have reviewed the articles from 1985 onward, reporting in vitro inhibition of E6. Recently, many computational studies have reported potent E6 inhibitors and these have also been reviewed. Subsequently, a critical analysis has been reported to cover the in vitro assay protocols and in vivo models to develop E6 inhibitors. A paragraph has been devoted to the role of public policy to fight CC employing vaccines and whether the vaccine against HPV has quenched the zeal to develop drugs against it. The review concludes with the challenges and the way forward.