4.6 Review

The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer

Journal

MILITARY MEDICAL RESEARCH
Volume 9, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s40779-022-00401-3

Keywords

HER2-positive (HER2+); Breast cancer; Targeted therapy; Tucatinib; Immunotherapy

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HER2 overexpression is common in breast cancer and is associated with poor prognosis. HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors have been used to treat HER2-positive breast cancer, but resistance mechanisms and limited treatment options after disease progression remain challenges. The recent FDA approval of tucatinib, a new tyrosine kinase inhibitor, for use in combination with immunotherapy and/or chemotherapy represents an important advancement in the treatment of advanced/metastatic HER2-positive breast cancer.
Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in approximately 15-20% of breast cancer cases. HER2 is a member of the epidermal growth factor receptor (EGFR) family with tyrosinase kinase activity, and its overexpression is linked to poor prognosis and shorter progression-free survival (PFS) and overall survival (OS). Among various treatment options, HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors (TKIs) have mostly been applied in recent decades to treat HER2-positive (HER2+) breast cancer patients. Although positive clinical outcomes were documented in both advanced disease and neoadjuvant settings, the development of resistance mechanisms to such approaches has been one of the major challenges with the continuous usage of these drugs. In addition, patients who experience disease progression after treatment with multiple HER2-targeted therapies often have limited treatment options. The Food and Drug Administration (FDA) has recently approved a new TKI (i.e., tucatinib) for use in combination with immunotherapy and/or chemotherapeutic agents for the treatment of advanced-stage/metastatic HER2+ breast cancer. This review highlights recent updates on the efficacy of tucatinib-based therapeutic approaches in experimental models as well as in the clinical settings of HER2+ breast cancer.

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