BRAF, KRAS and PIK3CA Mutation and Sensitivity to Trastuzumab in Breast Cancer Cell Line Model

Patra, Satyajit; Young, Vanesa; Llewellyn, Leslie; Senapati, Jitendra; Mathew, Jesil

doi:10.22034/APJCP.2017.18.8.2209

BRAF, KRAS and PIK3CA Mutation and Sensitivity to Trastuzumab in Breast Cancer Cell Line Model

Document Type : Research Articles

Authors

¹ Division of Biochemistry and Genetics American International Medical University Saint Lucia, United States.

² Florida Atlantic University, United States.

³ IMS and SUM Hospital, India.

⁴ Manipal College of Pharmaceutical Sciences, India.

10.22034/APJCP.2017.18.8.2209

Abstract

Studies show that approximately 20% of all breast cancer patients have a breast tumor that tests positive for Human Epidermal Growth Factor Receptor 2, otherwise known as the HER2 gene. As such, treatments for breast cancer usually include drugs that target HER2. The drug Trastuzumab is a recombinant antibody that has been approved by the FDA for the treatment of these HER2 positive breast cancers. However, researchers have found that mutations in associated genes, PIK3CA and KRAS, can cause the tumor to become resistant to Trastuzumab. The purpose of this article is to evaluate the sensitivity of the cancer cell lines to the drug Trastuzumab and investigate how this sensitivity is compromised by the PIK3CA, KRAS and BRAF gene mutations. Trastuzumab responsiveness was evaluated in breast cancer cell lines by treating the lines with an optimal concentration of the drug followed by a proliferation assay of the cell lines in the presence of monoclonal antibodies. We determined the optimum concentration of Trastuzumab to be 7 μg/well. The BRAF and KRAS mutated cell line, MDA-MB-231, showed the least sensitivity after being treated with trastuzumab when compared to the sensitivity of the PIK3CA mutated cell lines, MCF-7 and MDA-MB-361, and the KRAS/ BRAF/ PIK3CA cell line, MDA-MB-453. Clinical observations show that mutations in BRAF and KRAS genes in breast cancer cells do lower the responsiveness of Trastuzumab drug treatments.

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