Affiliations 

  • 1 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
  • 2 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
  • 3 Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, People's Republic of China
  • 4 Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor Darul Ehsan, Malaysia. reyhaneh.farghadani@monash.edu
  • 5 Graduate Institute of Biomedical Sciences, Institute of Biochemistry and Molecular Biology, Research Center for Cancer Biology, Cancer Biology and Precision Therapeutics Center, and Center for Molecular Medicine, China Medical University, Taichung, 406, Taiwan. dr.parham@mail.cmu.edu.tw
Cancer Metastasis Rev, 2024 Feb 27.
PMID: 38409546 DOI: 10.1007/s10555-024-10174-x

Abstract

Atezolizumab (TECENTRIQ®) and nivolumab (OPDIVO®) are both immunotherapeutic indications targeting programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 (PD-1), respectively. These inhibitors hold promise as therapies for triple-negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) and have demonstrated encouraging results in reducing the progression and spread of tumors. However, due to their adverse effects and low response rates, the US Food and Drug Administration (FDA) has withdrawn the approval of atezolizumab in TNBC and nivolumab in HCC treatment. The withdrawals of atezolizumab and nivolumab have raised concerns regarding their effectiveness and the ability to predict treatment responses. Therefore, the current study aims to investigate the immunotherapy withdrawal of PD-1/PD-L1 inhibitors, specifically atezolizumab for TNBC and nivolumab for HCC. This study will examine both the structural and clinical aspects. This review provides detailed insights into the structure of the PD-1 receptor and its ligands, the interactions between PD-1 and PD-L1, and their interactions with the withdrawn antibodies (atezolizumab and nivolumab) as well as PD-1 and PD-L1 modifications. In addition, this review further assesses these antibodies in the context of TNBC and HCC. It seeks to elucidate the factors that contribute to diverse responses to PD-1/PD-L1 therapy in different types of cancer and propose approaches for predicting responses, mitigating the potential risks linked to therapy withdrawals, and optimizing patient outcomes. By better understanding the mechanisms underlying responses to PD-1/PD-L1 therapy and developing strategies to predict these responses, it is possible to create more efficient treatments for TNBC and HCC.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.