Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance

Abstract

Read online

Despite advancements in understanding cancer pathogenesis and the development of many effective therapeutic agents, resistance to drug treatment remains a widespread challenge that substantially limits curative outcomes. The historical focus on genetic evolution under drug “pressure” as a key driver of resistance has uncovered numerous mechanisms of therapeutic value, especially with respect to acquired resistance. However, recent discoveries have also revealed a potential role for an ancient evolutionary balance between endogenous “viral” elements in the human genome and diverse factors involved in their restriction in tumor evolution and drug resistance. It has long been appreciated that the stability of genomic repeats such as telomeres and centromeres affect tumor fitness, but recent findings suggest that de-regulation of other repetitive genome elements, including retrotransposons, might also be exploited as cancer therapy. This review aims to present an overview of these recent findings.

Keywords

• transposable elements
• drug resistance
• epigenetic regulation
• restriction factors
• R-loops
• nucleic acid sensing