Novel treatment approaches utilizing antibody-drug conjugates in breast cancer
Andrew A Davis1, Jennifer Hesse2, Patrícia M R Pereira3
1Division of Oncology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA. aadavis@wustl.edu.
Abstract:
Antibody-drug conjugates (ADCs) are rapidly changing the way we treat patients with breast cancer. Despite this progress, many unanswered questions remain regarding the sequencing of different ADCs with similar payloads, optimal combinations, drug design strategies to limit off-target toxicities, biomarkers to define antigen positivity, and the use of ADCs in the neoadjuvant and adjuvant settings. In this review, we summarize novel ADC approaches in breast cancer treatment, including potential improvements in ADC payloads, linkers, targets, and drug delivery. We also evaluate novel strategies to combine ADCs with other agents, such as targeted drugs and immune checkpoint inhibitors. To improve patient selection, the development of quantitative biomarkers is reviewed, including HER2 mRNA, immunofluorescence-based assays, mass spectrometry, liquid biopsies, digital pathology, and molecular imaging-based approaches. Lastly, we evaluate the potential to incorporate ADCs into the early-stage setting, including evaluating currently published and ongoing clinical trials. This review highlights the potential for ADCs to shift the treatment paradigm in both the advanced and early-stage settings. We further demonstrate the complexity and challenges of improving ADCs to enhance targeting of tumor vulnerabilities while limiting toxicity through rationale drug development strategies to enhance the therapeutic window, linker technology, and payload variability to continue to improve outcomes for patients with breast cancer.
Insights
Antibody-drug conjugates (ADCs) are revolutionizing breast cancer treatment. This review explores advancements in ADC design, combinations, biomarkers, and early-stage applications to improve patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in breast cancer therapy.
- Despite progress, challenges remain in ADC sequencing, combination strategies, toxicity management, and patient selection.
Purpose of the Study:
- To review novel ADC approaches in breast cancer, encompassing payload, linker, target, and delivery improvements.
- To evaluate strategies for combining ADCs with other therapies and discuss biomarker development for patient selection.
- To assess the potential of ADCs in neoadjuvant and adjuvant breast cancer settings.
Main Methods:
- Literature review of current and emerging ADC technologies in breast cancer treatment.
- Analysis of strategies for ADC combination therapy and biomarker development.
- Evaluation of clinical trials investigating ADCs in early-stage breast cancer.
Main Results:
- Novel ADC designs, payloads, linkers, and targets are emerging to enhance efficacy and reduce toxicity.
- Quantitative biomarkers (e.g., HER2 mRNA, liquid biopsies, digital pathology) are crucial for optimizing patient selection.
- ADCs show promise for shifting the treatment paradigm in both advanced and early-stage breast cancer.
Conclusions:
- ADCs offer significant potential to improve breast cancer treatment outcomes.
- Continued innovation in ADC drug development, targeting, and biomarker strategies is essential to maximize therapeutic benefits and minimize toxicity.
- Integrating ADCs into early-stage treatment protocols may represent a future standard of care.
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