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; Raimondo, Lucia; Formisano, Luigi; Giuliano, Mario; DE PLACIDO, Sabino; Rosa, Roberta; Bianco, Roberto. - In: CANCER TREATMENT REVIEWS. - ISSN 0305-7372. - 41:10(2015), pp. 877-83-883. [10.1016/j.ctrv.2015.08.001]
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.