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

## TL;DR

This paper reviews new treatments for cervical cancer, including drugs that target blood vessels, antibodies that deliver toxic drugs, and immunotherapy, aiming to improve outcomes for advanced cases.

## Contribution

The paper provides an updated overview of emerging therapies and clinical trials for cervical cancer treatment.

## Key findings

- Drugs like Bevacizumab and Endostar improve survival in advanced cervical cancer.
- Immunotherapy targeting PD1, PD-L1, and CTLA4 is a promising treatment modality.
- Antibody-drug conjugates like Tisotumab Vedotin deliver toxic payloads directly to tumor cells.

## Abstract

Cervical cancer remains a frequently diagnosed cancer among women and a major cause of death, despite efforts to reduce its occurrence with the preventive vaccines. Thanks to a better understanding of the molecular processes that define cervical cancer, newer approaches to tackle this cancer have been developed to supplement the traditional surgery, chemotherapy, and radiation. These include drugs that target blood vessel growth, specific antibodies that deliver a toxic drug directly to the cancer site, and immunotherapy that mounts the body’s immune system against the cancer cells. In addition, therapeutic vaccines that can be administered after the development of local lesions are being investigated as an additional treatment possibility. This review aims to summarize these emerging therapies and ongoing clinical trials, highlighting advances in cervical cancer 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.