The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-β and PD-L1 Pathways

Frontiers in Oncology

Christian Valencia¹  Keiichi Fujiwara²  Isabelle Ray-Coquard³  Laureen S. Ojalvo³  Ana Oaknin⁴  Leslie Randall⁵  Michael J. Birrer⁶ 

[1]Development Institute, Inc., Billerica, MA, United States

[2]Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan

[3]

[4]EMD Serono Research &Gynaecological Cancer Program, Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, Spain

[5]Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States

[6]Winthrop P. Rockefeller Cancer Institute, University of Arkansas Medical School, Little Rock, AR, United States

关键词: cervical cancer;    HPV;    tumor microenvironment;    TGF-β;    PD-L1;   

DOI  :  10.3389/fonc.2022.814169

来源: DOAJ

【 摘 要 】

Cervical cancer is one of the most common and lethal cancers among women worldwide. Treatment options are limited in patients with persistent, recurrent, or metastatic cervical cancer, with <20% of women living >5 years. Persistent human papillomavirus (HPV) infection has been implicated in almost all cases of cervical cancer. HPV infection not only causes normal cervical cells to transform into cancer cells, but also creates an immunosuppressive environment for cancer cells to evade the immune system. Recent clinical trials of drugs targeting the PD-(L)1 pathway have demonstrated improvement in overall survival in patients with cervical cancer, but only 20% to 30% of patients show overall survival benefit beyond 2 years, and resistance to these treatments remains common. Therefore, novel treatment strategies targeting HPV infection–associated factors are currently being evaluated in clinical trials. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody that blocks PD-L1. Early clinical trials of bintrafusp alfa have shown promising results in patients with advanced cervical cancer.

【 授权许可】

Unknown