Embracing synthetic lethality of novel anticancer therapies

Abstract

Introduction: The significant challenge posed by cancer to human healthcare has led to the exploration of new approaches to combat it. Synthetic lethality (SL) is one such emerging area in the development of novel anticancer therapies. SL can be described as lethality (cell death) resulting from the combination of the two mutations, wherein the mutation in either of the two codependent genes in normal or cancer cells is viable. This concept is specifically being exploited in cancer research for selectively targeting specific tumor cells.

Areas covered: In this review, the authors summarize studies of SL-based novel anticancer therapies. The review highlights some of the selected advances in DNA damage response pathway-related SL pairs, particularly poly (ADP-ribose) polymerase (PARP) and SL pairs involved in mitochondrial death signaling pathways published in the last 3 years.

Expert opinion: Most of the currently used chemotherapeutic agents will destroy cells irrespective of whether they are cancer cells or fast growing normal cells; but SL is one of the approaches being developed with potential as a selective cancer therapy. PARP inhibitors, such as olaparib, are useful in BRCA mutated cancer cells and are also used in combination with other drug to enhance their efficacy. Research on PARP inhibitors is progressing at a good pace but there are still some significant challenges that must be addressed.

Keywords: Bcl-2; anticancer synthetic lethality pairs; apoptosis; olaparib; poly (ADP-ribose) polymerase inhibitors; synthetic lethality.