Antibody-drug conjugates in advanced lung cancer: Is this a new frontier?
Joshua E Reuss1, Samuel Rosner2, Benjamin P Levy3
1Georgetown Lombardi Comprehensive Cancer Center, Washington, DC.
Abstract:
Over the past decade, the lung cancer landscape has been dominated by targeted and immunotherapeutic approaches that have drastically shifted treatment paradigms for patients with advanced non-small cell lung cancer (NSCLC). Despite these scientific and clinical advances, there are still many unmet needs underscoring the importance of novel strategies. Antibody-drug conjugates (ADCs) represent one such strategy that is beginning to alter the therapeutic strategies for patients with advanced NSCLC. The rationale of ADCs is simple: selectively deliver cytotoxic payloads through an antibody-mediated process to target antigens expressed by cancer cells, sparing normal tissue and inflicting damage to tumors. Although this concept has been the leading view, preclinical and clinical observations are demonstrating that only a nascent mechanistic understanding of these agents exists. In this review, we discuss the underlying biology of ADCs and their structure and potential mechanisms of action, examine approved and promising ADC targets in lung cancer, and review emerging ADC targets and combinatorial strategies. Importantly, we address the unanswered questions surrounding ADCs in lung cancer, including biomarker selection, treatment sequencing, and mechanisms of resistance, as well as management of unique ADC-associated toxicities.
Insights
Antibody-drug conjugates (ADCs) offer a novel strategy for advanced non-small cell lung cancer (NSCLC) by delivering targeted cytotoxic payloads. Further research is needed to fully understand their mechanisms, optimize use, and manage toxicities in NSCLC treatment.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment has been revolutionized by targeted therapies and immunotherapies.
- Despite progress, significant unmet needs persist in managing advanced NSCLC.
- Antibody-drug conjugates (ADCs) are emerging as a promising therapeutic strategy for NSCLC.
Purpose of the Study:
- To review the biology, structure, and mechanisms of action of ADCs in NSCLC.
- To examine current and potential ADC targets and combinatorial strategies for NSCLC.
- To address critical unanswered questions regarding ADC use in NSCLC.
Main Methods:
- Literature review of preclinical and clinical studies on ADCs in NSCLC.
- Analysis of approved and investigational ADC targets and their associated antigens.
- Discussion of emerging strategies, resistance mechanisms, and toxicity management.
Main Results:
- ADCs selectively deliver cytotoxic payloads to cancer cells via antibody targeting.
- Current understanding of ADC mechanisms is nascent, requiring further investigation.
- Several ADC targets are approved or under investigation for NSCLC treatment.
Conclusions:
- ADCs represent a significant advancement in NSCLC therapy, offering targeted cytotoxicity.
- Further research is crucial to elucidate ADC mechanisms, identify optimal biomarkers, and refine treatment sequencing.
- Addressing resistance and managing ADC-specific toxicities are key to maximizing therapeutic benefit in NSCLC.
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