Single nucleotide polymorphisms Rs1045642 C>T genetic alteration in ATP Binding Cassette Subfamily B Member 1 role in increasing everolimus toxicity in metastatic breast cancer

Abstract

Breast cancer is one of the most devastating diseases in the world, the most diffused cancer in women. Despite the incredible progress made in the field, the mortality rate in the metastatic setting is still quite high. Among the different drugs used to treat this disease, the mTOR inhibitor everolimus is one of the most promising ones, that has been approved to be used together with exemestane in the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole, following the encouraging results coming from BOLERO-2 clinical trial showing a significant increase in progression-free-survival of patients compared to patients treated with exemestane and placebo. In this article we will discuss how the toxicity of this drug could be increased with Rs1045642 C>T genetic alteration in ATP Binding Cassette Subfamily B Member 1 (ABCB1), a pump that expels this drug from the cells, leading to a more inactive ABCB1. With an inactivation of ABCB1 more everolimus would linger within the cancer cells, exerting more of its anti-tumor work. Future diagnosis of genetic alteration of Rs1045642 C>T in ABCB1 could be pivotal for determining if patients would benefit more from everolimus.