Heart failure after myocardial infarction promotes mammary tumor growth via NGF–TRKA pathway

Epidemiological data suggest that patients with heart failure are at increased risk of developing cancer, but mechanistic links remain unclear. A study published in JACC: CardioOncology used a syngeneic mouse model to explore whether myocardial infarction (MI)–induced heart failure can drive mammary tumor growth.

Key findings. Female BALB/c mice with MI exhibited larger tumor volumes, higher tumor weight, and increased proliferation (Ki67+) after implantation of mammary tumor–derived 4T1 cells compared with sham-operated controls. RNA sequencing of tumor tissue revealed enrichment of pathways related to cell cycle progression and PI3K–AKT signaling.

Mechanistically, MI was associated with elevated circulating nerve growth factor (NGF) and upregulation of NGF expression in infarcted myocardium. This promoted phosphorylation of TRKA in tumor tissue, leading to activation of downstream AKT signaling and accelerated tumor cell proliferation. In vitro, NGF stimulation enhanced proliferation of 4T1 cells, while TRKA knockdown or pharmacological inhibition with GW441756 blocked these effects. Importantly, administration of GW441756 in vivo suppressed tumor growth in MI mice without affecting cardiac function.

Implications. The study provides experimental evidence that MI-induced heart failure can promote primary tumor growth through a humoral factor–mediated mechanism involving the NGF–TRKA axis. It also suggests that TRKA inhibition may represent a therapeutic strategy for breast cancer patients with comorbid heart failure after MI.

#CardioOncology #BreastCancer #HeartFailure #NGF #TRKA

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