Antibody-Drug Conjugates in Lung Cancer: Recent Advances and Implementing Strategies
Antonio Passaro1, Pasi A Jänne2, Solange Peters3
1Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan, Italy.
Abstract:
Antibody-drug conjugates (ADCs) are one of the fastest-growing oncology therapeutics, merging the cytotoxic effect of conjugated payload with the high specific ability and selectivity of monoclonal antibody targeted on a specific cancer cell membrane antigen. The main targets for ADC development are antigens commonly expressed by lung cancer cells, but not in normal tissues. They include human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, trophoblast cell surface antigen 2, c-MET, carcinoembryonic antigen-related cell adhesion molecule 5, and B7-H3, each with one or more specific ADCs that showed encouraging results in the lung cancer field, more in non-small-cell lung cancer than in small-cell lung cancer histology. To date, multiple ADCs are under evaluation, alone or in combination with different molecules (eg, chemotherapy agents or immune checkpoint inhibitors), and the optimal strategy for selecting patients who may benefit from the treatment is evolving, including an improvement of biomarker understanding, involving markers of resistance or response to the payload, besides the antibody target. In this review, we discuss the available evidence and future perspectives on ADCs for lung cancer treatment, including a comprehensive discussion on structure-based drug design, mechanism of action, and resistance concepts. Data were summarized by specific target antigen, biology, efficacy, and safety, differing among ADCs according to the ADC payload and their pharmacokinetics and pharmacodynamics properties.
Insights
Antibody-drug conjugates (ADCs) are emerging oncology therapeutics targeting lung cancer antigens. This review details ADC development, mechanisms, and future perspectives for improved lung cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) represent a rapidly advancing class of cancer therapeutics.
- ADCs combine monoclonal antibodies for targeted cancer cell delivery with potent cytotoxic payloads.
- Key targets in lung cancer include HER2, HER3, TROP2, c-MET, CEACAM5, and B7-H3.
Purpose of the Study:
- To review current evidence and future directions for ADCs in lung cancer treatment.
- To discuss ADC structure-based design, mechanisms of action, and resistance pathways.
- To summarize data on ADC efficacy, safety, and target-specific characteristics.
Main Methods:
- Literature review of existing studies on ADCs for lung cancer.
- Analysis of ADC development targeting specific lung cancer antigens.
- Synthesis of data on ADC pharmacokinetics, pharmacodynamics, efficacy, and safety.
Main Results:
- Multiple ADCs targeting various antigens show promise, particularly in non-small-cell lung cancer.
- Ongoing research explores ADC combinations with chemotherapy and immune checkpoint inhibitors.
- Biomarker understanding is crucial for optimizing patient selection and predicting response.
Conclusions:
- ADCs offer a promising therapeutic strategy for lung cancer, with ongoing advancements in design and application.
- Further research into resistance mechanisms and predictive biomarkers is essential for clinical success.
- Personalized treatment approaches leveraging ADCs are expected to improve patient outcomes.
