Argentina: Drug resistance in breast cancer

Acyl-CoA synthetase-4 is implicated in drug resistance in breast cancer cell lines involving the regulation of energy-dependent transporter expression

Ulises Daniel Orlando, Ana Fernanda Castillo, Mayra Agustina Ríos Medrano,

Angela Rosaria Solano, Paula Mariana Maloberti & Ernesto Jorge Podesta | Biomedical Research Institute, INBIOMED (UBA, CONICET), Department of Biochemistry, School of Medicine, University of Buenos Aires, CABA C1121ABG, Argentina | 2018 | Biochemical Pharmacology; vol. 159, pp. 52-63

Research into therapy resistance provides valuable findings on how to avoid drug resistance in cancer cells. Acyl-CoA synthetase-4 (ACSL4) is an enzyme that participates in negative regulation of the estrogen receptor α (ERα) and hormone therapy resistance in breast and prostate cancer. Breast cancer therapy resistance is also found in ATP-binding cassette (ABC) transportes which detect and eject anti-cancer drugs from cells. In this study, the role of ACSl4 and the underlying mechanism of the ABC transporters was studied to understand their roles in therapeutic resistance. RT-qPCR analysis of mRNA expression levels found high level expression of genes ABCG2, ABCG8 and ABCG4 in cells repressing ACSL4 and thus further validate the correlation between these genes and ACSL4 expression. The study concluded that ACSL4 may be a novel therapeutic target that regulates the expression of the ABC transporter through the mTOR pathway to restore drug sensitivity.