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Pioneering the Way: The Revolutionary Potential of Antibody–Drug Conjugates in NSCLC

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Opinion statement

Despite targeted therapy and immunotherapy being recognized as established frontline treatments for advanced non-small cell lung cancer (NSCLC), the unavoidable development of resistance and disease progression poses ongoing challenges. Antibody–drug conjugates (ADCs) offer a potent treatment option for NSCLC through the specific delivery of cytotoxic agents to tumor cells that display distinct antigens. This review delves into the latest evidence regarding promising ADC agents for NSCLC, focusing on their targets, effectiveness, and safety assessments. Additionally, our study provides insights into managing toxicities, identifying biomarkers, devising methods to counter resistance mechanisms, tackling prevailing challenges, and outlining prospects for the clinical implementation of these innovative ADCs and combination regimens in NSCLC.

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Abbreviations

ADC:

Antibody-drug conjugate

NSCLC:

Non-small cell lung cancer

DAR:

Drug-antibody ratio

ICIs:

Immune checkpoint inhibitors

TKI:

Tyrosine kinase inhibitor

mAb:

Monoclonal antibody

IgG:

Immunoglobulin G

CEACAM5:

Carcinoembryonic antigen-related cell adhesion molecule 5

TF:

Tissue factor

ORR:

Overall response rate

TNBC:

Triple-negative breast cancer

SCLC:

Small cell lung cancer

PR:

Partial response

DOR:

Duration of response

CBR:

Clinical benefit rate

ITT:

Intention-to-treat

PFS:

Progression-free survival

OS:

Overall survival

TROP2:

Trophoblast cell surface antigen 2

HER3:

Human epidermal growth factor receptor 3

TEAEs:

Treatment-emergent adverse events

TPS:

Tumor proportion score

SD:

Stable disease

NPLD:

Non-pegylated liposomal doxorubicin

SG:

Sacituzumab govitecan

TRAEs:

Treatment-related adverse events

FDA:

The United States Food and Drug Administration

CEACAM5:

Carcinoembryonic antigen-related cell adhesion molecule 5

ESC:

European Society of Cardiology

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Funding

This work was supported by the National Natural Science Foundation of China (grant number: 82270940).

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Authors and Affiliations

  1. Department of Geriatric Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China

    Xiehui Chen MD

  2. Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China

    Changchun Zeng MD

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  1. Xiehui Chen MD
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XH C and CC Z conceived and designed the work. XH C drafted the manuscript. XH C and CC Z revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Changchun Zeng MD.

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Chen, X., Zeng, C. Pioneering the Way: The Revolutionary Potential of Antibody–Drug Conjugates in NSCLC. Curr. Treat. Options in Oncol. 25, 556–584 (2024). https://doi.org/10.1007/s11864-024-01196-2

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