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Comprehensive assessment of TECENTRIQ® and OPDIVO®: analyzing immunotherapy indications withdrawn in triple-negative breast cancer and hepatocellular carcinoma

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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 However, due to their adverse effects and low response rates, the US Food and Drug Administration (FDA) has withdrawn the approval of atezolizumab in TNBC and nivolumab in HCC treatment.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of the PD-1 receptor and its ligands, the interactions between PD-1 and PD-L1, and their interactions with the withdrawn antibodies (atezolizumab and nivolumab) as well as PD-1 and PD-L1 modifications.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.

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Data availability

All data used in the present review are available at clinicaltrial.gov and FDA.gov.

Abbreviations

ADA:

Anti-drug antibodies

ADCC:

Antibody-dependent cellular cytotoxicity

AMPK:

Adenosine monophosphate-activated protein kinase

c-CBL:

Casitas B-lineage lymphoma

CDR:

Complementarity determining regions

DOR:

Duration of response

EGFR:

Epidermal growth factor receptor

FDA:

The United States food and drug administration

GSK:

Glycogen synthase kinase

HCC:

Hepatocellular carcinoma

IgV:

Immunoglobulin-variable

ICB:

Immune checkpoint blockade

ITIM:

Immunoreceptor tyrosine‐based inhibition motif

ITSM:

Immunoreceptor tyrosine‐based switch motif

NEK:

Never in mitosis gene A (NIMA)-related kinase

NK:

Natural killer

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PD-L1:

Programmed cell death 1 ligand 1

PD-1:

Programmed cell death protein 1

PFS:

Progression-free survival

RTK:

Receptor tyrosine kinase

SHP:

Src homology region 2 (SH2)-containing protein tyrosine phosphatase

SPOP:

The substrate-binding adaptor speckle-type POZ protein

TEAE:

Treatment-related adverse event

USP:

Ubiquitin-specific peptidases

TAM:

Tumor-associated macrophage

TNBC:

Triple-negative breast cancer

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Acknowledgements

The authors would like to acknowledge that the Figures presented in this work were created using BioRender, utilizing a licensed account purchased by Parham Jabbarzadeh Kaboli.

Funding

Article processing charge for the present review was paid by Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia for Reyhaneh Farghadani.

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Author notes

  1. Ghazaal Roozitalab and Behnaz Abedi contributed equally.

Authors and Affiliations

  1. Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran

    Ghazaal Roozitalab

  2. Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

    Behnaz Abedi

  3. Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, People’s Republic of China

    Saber Imani

  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

  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

    Parham Jabbarzadeh Kaboli

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Contributions

Conceptualization, P.J.K.; Writing – Original Draft, G.R., B.A., and P.J.K.; Writing – Review & Editing, P.J.K., S.I., and R.F.; Visualization, G.R. and B.A; Funding Acquisition, R.F.; Supervision, P.J.K.

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Roozitalab, G., Abedi, B., Imani, S. et al. Comprehensive assessment of TECENTRIQ® and OPDIVO®: analyzing immunotherapy indications withdrawn in triple-negative breast cancer and hepatocellular carcinoma. Cancer Metastasis Rev (2024). https://doi.org/10.1007/s10555-024-10174-x

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