HER2 positive breast cancer is characterized by the low survival rate in the metastatic patients.
Development of resistance and disease-relapse are the major problems associated with the
currently available therapies for HER2 positive breast cancer. There are two major targeted therapies
for HER2 positive breast cancer viz. monoclonal antibodies and tyrosine-kinase inhibitors, and both
of these therapies have their advantages and limitations. To address the limitations associated with
the existing therapies, use of antibodies and TKIs as combination therapy proved to be more effective.
Various chemical modifications can be performed on tyrosine-kinase inhibitors to develop
novel ligands with increased selectivity for HER2 kinase. A number of tyrosine-kinase inhibitors are
in various phases of clinical trials for the treatment of HER2 positive breast cancer. In the current
review article, recent developments on various HER2 tyrosine-kinase inhibitors have been reported.
Various structurally different scaffolds bind to the HER2 receptor and exhibit potent anti-cancer activities.
The structural and pharmacophoric requirements of the scaffolds are discussed in detail so as
to discover effective drug candidates for the treatment of HER2 positive breast cancer.
Keywords: Breast cancer, HER1/HER2, Tyrosine kinase inhibitors, Drug resistance, Monoclonal antibodies, Trastuzumab.
Rights & PermissionsPrintExport