Targeted therapies have been approved for various malignancies but the acquisition of resistance remains a substantial challenge in the clinical management of advanced cancers. Twenty-five per cent of breast cancers overexpress ErbB2/HER2, which confers a more aggressive phenotype and is associated with a poor prognosis. HER2-targeting therapies (trastuzumab, pertuzumab, TDM1 and lapatinib) are available, but a significant fraction of HER2-positive breast cancers eventually relapse or progress. This suggests that acquired or intrinsic resistance enables escape from HER2 inhibition. This review focuses on mechanisms of intrinsic/acquired resistance to lapatinib identified in preclinical and clinical studies. A better understanding of these mechanisms could lead to novel predictive markers of lapatinib response and to novel therapeutic strategies for breast cancer patients.

Mechanisms of lapatinib resistance in HER2-driven breast cancer

D'AMATO, VALENTINA;FORMISANO, LUIGI;GIULIANO, MARIO;DE PLACIDO, SABINO;ROSA, ROBERTA;BIANCO, ROBERTO
2015

Abstract

Targeted therapies have been approved for various malignancies but the acquisition of resistance remains a substantial challenge in the clinical management of advanced cancers. Twenty-five per cent of breast cancers overexpress ErbB2/HER2, which confers a more aggressive phenotype and is associated with a poor prognosis. HER2-targeting therapies (trastuzumab, pertuzumab, TDM1 and lapatinib) are available, but a significant fraction of HER2-positive breast cancers eventually relapse or progress. This suggests that acquired or intrinsic resistance enables escape from HER2 inhibition. This review focuses on mechanisms of intrinsic/acquired resistance to lapatinib identified in preclinical and clinical studies. A better understanding of these mechanisms could lead to novel predictive markers of lapatinib response and to novel therapeutic strategies for breast cancer patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/615670
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