Medicinal Research Reviews

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

AbstractAn 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.

Fluorescent imaging probes for in vivo ovarian cancer targeted detection and surgery

AbstractOvarian cancer is the most lethal gynecological cancer, with a survival rate of approximately 40% at five years from the diagno. The first‐line treatment consists of cytoreductive surgery combined with chemotherapy (platinum‐ and taxane‐based drugs). To date, the main prognostic factor is related to the complete surgical resection of tumor lesions, including occult micrometastases. The presence of minimal residual diseases not detected by visual inspection and palpation during surgery significantly increases the risk of disease relapse. Intraoperative fluorescence imaging systems have the potential to improve surgical outcomes. Fluorescent tracers administered to the patient may support surgeons for better real‐time visualization of tumor lesions during cytoreductive procedures. In the last decade, consistent with the discovery of an increasing number of ovarian cancer‐specific targets, a wide range of fluorescent agents were identified to be employed for intraoperatively detecting ovarian cancer. Here, we present a collection of fluorescent probes designed and developed for fluorescence‐guided ovarian cancer surgery. Original articles published between 2011 and November 2022 focusing on fluorescent probes, currently under preclinical and clinical investigation, were searched in PubMed. The keywords used were targeted detection, ovarian cancer, fluorescent probe, near‐infrared fluorescence, fluorescence‐guided surgery, and intraoperative imaging. All identified papers were English‐language full‐text papers, and probes were classified based on the location of the biological target: intracellular, membrane, and extracellular.