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Review
. 2023 Apr 20;30(4):4329-4350.
doi: 10.3390/curroncol30040330.

'Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer-An Updated Review

Saurav Verma  1   2 , Daniel Breadner  1   2 , Jacques Raphael  1   2
Affiliations
Review

'Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer-An Updated Review

Saurav Verma et al. Curr Oncol. .

Abstract

Antibody-Drug conjugates (ADCs) are a relatively new class of drugs with a promise to improve the outcomes in specific cancers. By delivering the cytotoxic agent to tumor cells expressing specific antigens, ADCs achieve a better therapeutic index and more potency. ADCs have been approved for several hematological and solid malignancies, including breast, urothelial and gastric carcinoma. Recently, trastuzumab deruxtecan (TDXd) was the first ADC approved for previously treated metastatic HER2-mutant non-small cell lung cancer (NSCLC). Many promising ADCs are in the pipeline for clinical development in non-small cell lung cancer, including sacituzumab govitecan, patritumab deruxtecan, datopotamab deruxtecan and tusamitamab ravtansine. There is a hope that these drugs would cater to the unmet need of specific patient populations, including patients with currently untargetable mutations. We hope these drugs, e.g., TROP2 targeted ADCs, will also give more options for therapy in NSCLC to improve outcomes for patients. In this comprehensive review, we will be discussing the recent evidence including targets, efficacy and the safety of newer ADC candidates in NSCLC. We will also briefly discuss the specific toxicities, novel biomarkers, overcoming resistance mechanisms, challenges and the way forward, as these new ADCs and combinations find a way into the clinical practice.

Keywords: ADCs; Antibody-Drug conjugate; non-small cell lung cancer (NSCLC).

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Conflict of interest statement

D.B. has accepted honoraria for advisory boards and/or speaking fees from Astra Zeneca, Bristol-Myers Squibb, Takeda, Merck, Bayer and Amgen. J.R. accepted honoraria for advisory boards from Astra Zeneca, Merck, Novartis and Lilly Oncology.

Figures

Figure 1
Figure 1
Structure of ADCs.
Figure 2
Figure 2
Mechanism of action of ADCs.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Fu Z., Li S., Han S., Shi C., Zhang Y. Antibody drug conjugate: The “biological missile” for targeted cancer therapy. Signal Transduct. Target. Ther. 2022;7:93. doi: 10.1038/s41392-022-00947-7. - DOI - PMC - PubMed
    1. De Cecco M., Galbraith D.N., McDermott L.L. What makes a good Antibody-Drug conjugate? Expert Opin. Biol. Ther. 2021;21:841–847. doi: 10.1080/14712598.2021.1880562. - DOI - PubMed
    1. Pysz I., Jackson P.J.M., Thurston D.E. Introduction to Antibody-Drug Conjugates (ADCs) In: Thurston D.E., Jackson P.J.M., editors. Cytotoxic Payloads for Antibody—Drug Conjugates [Internet] The Royal Society of Chemistry; London, UK: 2019. [(accessed on 10 April 2023)]. pp. 1–30. Available online: https://books.rsc.org/books/book/725/chapter/444646/Introduction-to-Anti....
    1. Coleman N., Yap T.A., Heymach J.V., Meric-Bernstam F., Le X. Antibody-drug conjugates in lung cancer: Dawn of a new era? NPJ Precis Oncol. 2023;7:5. doi: 10.1038/s41698-022-00338-9. - DOI - PMC - PubMed

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