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Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models
Regina Padmanabhan1,2, Hadeel Shafeeq Kheraldine2,3, Nader Meskin1
1Department of Electrical Engineering, Qatar University, 2713 Doha, Qatar.
Abstract:
Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.
Insights
This review explores HER2-targeted therapies and immune checkpoint inhibitors for HER2-positive breast cancer. It highlights the need for improved treatments to overcome resistance and enhance patient outcomes.
Area of Science:
- Oncology
- Immunology
- Mathematical Biology
Background:
- Breast cancer remains a leading cause of mortality in women globally.
- HER2-positive and triple-negative subtypes are particularly aggressive.
- Current HER2-targeted therapies improve outcomes but face challenges with relapse and treatment response.
Purpose of the Study:
- To review advancements in HER2-positive breast cancer management.
- To examine the interplay between HER2-targeted therapies and the PD-1/PD-L1 immune checkpoint axis.
- To explore mathematical models for analyzing HER2-positive breast cancer dynamics and immunotherapy.
Main Methods:
- Literature review of HER2-targeted therapies and immunomodulation strategies.
- Analysis of the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis in breast cancer.
- Review of mathematical models relevant to HER2-positive breast cancer and immune checkpoint inhibitors.
Main Results:
- HER2-targeted therapies have improved outcomes for HER2-positive breast cancer.
- Immune checkpoint pathways, like PD-1/PD-L1, are crucial in cancer evasion and offer therapeutic targets.
- Mathematical models can provide theoretical insights into cancer dynamics and treatment efficacy.
Conclusions:
- Combining HER2-targeted therapies with immunomodulation strategies shows promise for overcoming treatment resistance.
- Understanding the PD-1/PD-L1 axis is critical for enhancing breast cancer immunotherapy.
- Mathematical modeling can aid in optimizing treatment strategies for HER2-positive breast cancer.
