Three decades of basic research have largely elucidated the oncogenic mechanisms of human papilloma virus (HPV). HPV protein E5 achieves a takedown of antigen presentation to evade immune evasion while also impairing the ubiquitin turnover of EGFR. HPV E6 and E7 causes turnover of key tumor suppressor genes, p53 and PTPN13, and Rb1 and PTPN14, respectively. The signaling pathway consequences and resulting transcriptional reorganization that results in malignant behavior is discussed regarding the complex, self-perpetuating network of HPV. The potential utility of network-targeting combination therapy by re-purposing rimantidine, withaferin A, and curcumin to rescue the tumor suppressor proteins and re-establish immune recognition is discussed as a strategy to achieve deactivation of the malignant network that leads to collapse of the disease and reversal of therapeutic resistance. Investigation of this re-purposing regimen to block hypoxia by achieving cell cycle arrest could permit the use of lower doses of radiation that have potential to enhance treatment efficacy and survival while also decreasing the long-term side effects of radiotherapy.
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Journal of Integrative Oncology received 495 citations as per Google Scholar report
