Antibody-Drug Conjugates in Breast Cancer: The Road Towards Biologically-Informed Selection and Sequencing
Tess A O'Meara1,2, Paolo Tarantino3,4,5,6,7, Stefania Morganti3,4,5,6,7
1Susan F. Smith Center for Women's Cancers, Breast Oncology Program, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA. tess_omeara@dfci.harvard.edu.
Purpose Of Review:
In this review, we discuss evidence supporting the use of antibody-drug conjugates (ADCs) in breast cancer treatment, describe novel ADCs and combination regimens under development, and examine our current understanding of resistance mechanisms and biomarkers to guide ADC selection and sequencing.
Recent Findings:
Three ADCs have proven benefit in patients with metastatic breast cancer: trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG). There are over two hundred investigational ADCs on the horizon, as pre-clinical studies work to identify novel ADC targets and structures. In this new frontier, translational efforts are underway to personalize the use of ADCs, including refining HER2 quantification and elucidating genetic, epigenetic, and post-translational mechanisms of resistance. ADCs have provided important treatment options for patients with breast cancer. As patients become eligible for more than one ADC, there is an unmet need to identify the appropriate timing and sequence of these therapies to maximize their efficacy.
Insights
Antibody-drug conjugates (ADCs) offer new breast cancer treatment options. Research is ongoing to develop novel ADCs and understand resistance mechanisms for personalized therapy selection.
Area of Science:
- Oncology
- Pharmacology
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in targeted cancer therapy.
- Their application in breast cancer treatment has expanded, offering new hope for patients with metastatic disease.
Purpose of the Study:
- To review current evidence supporting ADCs in breast cancer treatment.
- To describe novel ADCs and combination regimens in development.
- To examine resistance mechanisms and biomarkers for guiding ADC selection and sequencing.
Main Methods:
- Review of existing literature and pre-clinical studies on ADCs for breast cancer.
- Analysis of ongoing clinical trials for novel ADC development.
- Investigation into mechanisms of ADC resistance and relevant biomarkers.
Main Results:
- Three ADCs—trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG)—have demonstrated efficacy in metastatic breast cancer.
- Over 200 investigational ADCs are in development, targeting novel structures and targets.
- Personalization efforts include refining HER2 quantification and understanding resistance mechanisms (genetic, epigenetic, post-translational).
Conclusions:
- ADCs are crucial treatment options for breast cancer patients.
- An unmet need exists for optimizing the timing and sequence of multiple ADC therapies.
- Further research into resistance and biomarkers will enhance personalized ADC selection and sequencing.
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