Key result
Exercise enhances HER2-targeted breast cancer therapies and overcomes resistance by downregulating HER2/PI3K signaling and CD44.
Why the study?
Despite advances in HER2-targeted therapies and CSC-directed agents, resistance remains a major barrier in breast cancer.
Does exercise disrupt HER2/CD44-driven therapy resistance and overcome cardiotoxicity in breast cancer?
Does exercise disrupt HER2/CD44-driven therapy resistance and overcome cardiotoxicity in breast cancer?
Exercise may serve as an adjuvant precision medicine strategy to reprogram the tumor-immune microenvironment and overcome therapy resistance and cardiotoxicity in breast cancer.
May support exercise to overcome HER2 resistance and cardiotoxicity; leaves open prospective trials for confirmation.
Despite advances in HER2-targeted therapies and CSC-directed agents, resistance remains a major barrier in breast cancer. Synthesize evidence for exercise as a precision strategy to disrupt HER2/CD44-driven resistance circuits. Preclinical and clinical data demonstrate that physical activity: (1) downregulates HER2/PI3K signaling via myokine-mediated pathways (IL-6/SPARC), (2) reduces CD44 through NK-dependent immune surveillance, and (3) synergizes with biologics to overcome cardiotoxicity and chemoresistance. Molecular subtype-specific exercise prescriptions are defined. Exercise reprograms the tumor-immune microenvironment to target therapy-resistant pathways, establishing a paradigm for exercise as adjuvant precision medicine.
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Haghi et al. (2026) studied this question. Exercise downregulates HER2/PI3K signaling and reduces CD44, enhancing the efficacy of HER2-targeted therapies and overcoming therapy resistance in breast cancer.
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