Journal article

Neoadjuvant neratinib promotes ferroptosis and inhibits brain metastasis in a novel syngeneic model of spontaneous HER2( ve) breast cancer metastasis

Aadya Nagpal, Richard P Redvers, Xiawei Ling, Scott Ayton, Miriam Fuentes, Elnaz Tavancheh, Irmina Diala, Alshad Lalani, Sherene Loi, Steven David, Robin L Anderson, Yvonne Smith, Delphine Merino, Delphine Denoyer, Normand Pouliot



BACKGROUND: Human epidermal growth factor receptor-2 (HER2)-targeted therapies prolong survival in HER2-positive breast cancer patients. Benefit stems primarily from improved control of systemic disease, but up to 50% of patients progress to incurable brain metastases due to acquired resistance and/or limited permeability of inhibitors across the blood-brain barrier. Neratinib, a potent irreversible pan-tyrosine kinase inhibitor, prolongs disease-free survival in the extended adjuvant setting, and several trials evaluating its efficacy alone or combination with other inhibitors in early and advanced HER2-positive breast cancer patients are ongoing. However, its efficacy as a first-line thera..

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Awarded by National Breast Cancer Foundation

Awarded by National Health & Medical Research Council (NHMRC)

Awarded by Cancer Australia

Funding Acknowledgements

This work was supported in part by a project grants from the National Breast Cancer Foundation (#IN-16-036) to NP, SL and RLA and IIRS-19-046 to NP, SA, DD, RLA and SL; a Lew Carty Foundation grant to SD; a La Trobe University Research Focus Area grant to NP; a National Health & Medical Research Council (NHMRC #1050384) to RLA; a Career Fellowship from the National Breast Cancer Foundation (NBCF) to RLA; and a Cancer Australia grant (#1067045) to RLA and NP. AN and MF were supported by La Trobe University Post Graduate Research Scholarships (LTUPRS/LTUFFRS). ET was supported by a humanitarian scholarship from the College of Health, Science and Engineering, La Trobe University.