Molecular Targets of Cervical Cancer and Its Microenvironment: Advances in Treatment

Cervical cancer remains one of the most commonly diagnosed cancers in women worldwide, with an elevated number of associated annual deaths, even though effective preventive vaccines are available. The pathophysiology of cervical cancer is well understood, with high-risk HPV as the main culprit in carcinogenesis, in addition to cell proliferation signaling alteration and tumor immune microenvironment modulation. This understanding of the disease's molecular signatures has led to the development of several lines of treatment, especially for advanced, recurrent, persistent, or metastatic disease. For instance, Bevacizumab, a monoclonal antibody targeting angiogenesis factors, as well as Endostar, a recombinant human endostatin, have been studied and shown to improve survival in advanced disease. In contrast, anti-angiogenic Tyrosine Kinase Inhibitors had limited efficacy. Furthermore, antibody-drug conjugates such as Tisotumab Vedotin allow to deliver a highly toxic payload directly to the tumor site by binding to tissue factor, which is highly expressed in cervical tumor cells. Moreover, immunotherapy has emerged as a key treatment modality in cervical cancer by inhibiting immune checkpoint inhibitors (PD1, PD-L1, and CTLA4). In addition, therapeutic vaccines have been investigated for the treatment of localized disease by enhancing cell-mediated immunity against E6 and E7 proteins. However, more robust clinical trials are needed before these vaccines can be effectively and safely used clinically. Finally, several ongoing trials are currently evaluating new therapeutic modalities and combinations of the currently available tools in the cervical cancer treatment armamentarium.