Novel therapeutic strategies for targeting E6 and E7 oncoproteins in cervical cancer

Cervical cancer is the fourth most common cause of cancer-related mortality among women worldwide. The main aetiological factor for developing cervical cancer is the persistent infection of Human papillomavirus (HPV). The E6 and E7 oncoproteins produced by HPV mainly contribute to the carcinogenic process by inhibiting the function of tumour suppressor genes. The E6 protein causes degradation of p53 leading to impaired cellular stress response. In contrast, the E7 protein impairs the activity of retinoblastoma protein (pRb) resulting in continuous cell cycle propagation. Even though screening programmes and prophylactic vaccination have reduced the incidence of cervical cancer, the disease burden is still high, especially in low socioeconomic countries. Treatment of cervical cancer involves a multimodal strategy incorporating surgery, chemotherapy, and radiotherapy. Most of these management approaches use invasive techniques and are associated with adverse effects. Drug resistance is observed over time with chemotherapeutic agents. Hence there is a crucial need for developing novel targeted treatment strategies for cervical cancer. The E6 and E7 viral oncoproteins are continuously expressed in HPV infected cells making them ideal targets for developing therapies. Therapeutic DNA vaccines, gene therapy involving RNA interference technology, and CRISPR are currently under intensive study. These technologies represent a productive and promising approach for the future treatment of cervical cancer. Moreover, several new compounds demonstrate significant anti-cancer effects against cervical cancer. This review provides an updated account of therapeutic strategies currently under research targeting the E6 and E7 viral oncoproteins.