Cancer cells acquire resistance to anticancer drugs: An update

Abstract

The efficacy of cancer chemotherapy is often affected by the emergence of resistant can­cer cells. While biochemical and pharmaco­logical mechanisms have been proposed to ex­plain chemo­resistance, the genes involved in this process have not been fully identified. We previ­ously used genomic DNA microarrays and quantitative RT-PCR to identify the genes associ­ated with resistance to chemotherapeutic drugs, particularly to the genotoxic agent cispla­tin. Notably, knockdown of the cisplatin resistance (CPR) genes that we identified was shown to reduce chemoresistance and to suppress the growth of tumor xenographs in cispla­tin-treated mice, indicating that the newly identified CPR genes may represent potential ther­apy candidates to limit chemo­resistance and to improve the efficacy of anticancer drugs. In addi­tion to genetic mutations, re­searchers have found that epigenetic changes and alternative splic­ing of specific genes may also allow cancer cells to become resistant to chemotherapeu­tic drugs. In this article, the au­thors present an overview of the latest findings in this field, includ­ing genetic changes, epige­netic changes and alternative splicing.

Keywords

• alternative splicing
• cisplatin
• chemoresistance
• DNA microarray
• epigenetic modifica-tions