Potential of afatinib in the treatment of patients with HER2-positive breast cancer

Breast Cancer : Targets and Therapy
Elena GeunaGiorgio Valabrega

Abstract

In the absence of treatment, overexpression of the human epidermal growth factor receptor 2 (HER2) predicts a poor prognosis in breast cancer. In the last decade, monoclonal antibodies and small molecule tyrosine kinase inhibitors have significantly improved the outcome of HER2-positive breast cancer patients. However, tumor resistance and toxicities often limit the use of these therapies. For this reason, there is a compelling need for further investigation of new targeted therapies, such as afatinib, an oral irreversible pan inhibitor of the epidermal growth factor receptor (EGFR) family. This compound covalently interacts with tyrosine kinase domains, which are deeply involved in signal transduction leading to cell proliferation and protection from apoptosis. Afatinib has been studied in several Phase I clinical trials in advanced solid tumors. These trials have shown encouraging clinical activity and manageable side effects when afatinib is used either as a single agent or in combination with chemotherapy, with cutaneous adverse events and diarrhea being the most frequently observed toxicities. This review will focus on afatinib's clinical activity and will discuss ongoing clinical studies in HER2-positive breast cancer pat...Continue Reading

Citations

Aug 29, 2013·Drugs·Rosselle T Dungo, Gillian M Keating
Oct 7, 2014·Current Breast Cancer Reports·Ciara C O'Sullivan, Karen L Smith
Sep 25, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Richard L SchroederJayalakshmi Sridhar
Nov 1, 2016·Breast Cancer : the Journal of the Japanese Breast Cancer Society·V L MaruthanilaJibon Kotoky
Jul 7, 2018·Drug Delivery and Translational Research·Sumayah Al-MahmoodTamara Minko

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