HER2 is a tyrosine kinase receptor whose overexpression is seen significantly in breast cancer and has been reported in approximately 25% of breast cancer cases. Significantly, HER2 amplification and overexpression predicts lower overall survival and HER2 overexpressing tumors exhibit decreased response to adjuvant therapy.  Although, the HER2 targeting therapeutic antibody, trastuzumab (Herceptin) is currently in clinical use, up to 88% of patients with HER2 positive breast cancer are resistant to single-agent tratuzumab.  The tratuzumab resistant oncogenic HER2Δ16 isoform has been found to be preferentially expressed in aggressive metastatic breast cancer. Tyrosine kinase inhibitors can be effective in the treatment of HER2-positive metastatic breast cancers as they can inhibit both the truncated HER2 (p95HER2 and HER2Δ16) and the full length HER2. Utilizing naphthoquinone derivatives which have shown positive results in the inhibition of HER2, development of similar compounds have been the main focus of this research. The developed compounds have yielded promising results, with the representative compound showing excellent inhibition of triple negative, trastuzumab sensitive and trastuzumab resistant breast cancer cell lines.

Synthesis and evaluation of naphthoquinone derivatives as inhibitors for HER2-positive breast cancer

251st National Meeting (2016)

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