Exercise as Precision Medicine: Targeting HER2/CD44-Driven Therapy Resistance in Breast Cancer (A Mini Review)

Area of Science:

• Oncology
• Immunology
• Exercise Physiology

Background:

• Therapeutic resistance to HER2-targeted agents and CSC-directed therapies remains a significant challenge in breast cancer treatment.
• Understanding resistance mechanisms is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To synthesize evidence supporting exercise as a precision strategy to overcome HER2/CD44-driven resistance in breast cancer.
• To define molecular subtype-specific exercise prescriptions.
• To establish exercise as an adjuvant precision medicine approach.

Main Methods:

• Review of preclinical and clinical data on the effects of physical activity on breast cancer resistance pathways.
• Analysis of myokine-mediated pathways (IL-6/SPARC) involved in HER2/PI3K signaling.
• Investigation of NK-dependent immune surveillance in CD44 reduction.
• Evaluation of exercise in synergy with biologics to mitigate cardiotoxicity and chemoresistance.

Main Results:

• Physical activity downregulates HER2/PI3K signaling through myokine pathways (IL-6/SPARC).
• Exercise reduces CD44 expression via NK-cell-mediated immune surveillance.
• Exercise synergizes with biologics, improving tolerance and overcoming chemoresistance.
• Molecular subtype-specific exercise regimens were defined.

Conclusions:

• Exercise acts as a potent adjuvant therapy by reprogramming the tumor-immune microenvironment.
• Physical activity disrupts HER2/CD44-driven resistance circuits, enhancing the effectiveness of targeted therapies.
• Exercise represents a novel paradigm for precision medicine in breast cancer management.