Synthetic Lethality to Overcome Cancer Drug Resistance

L.      Porcelli; A.      E. Quatrale; P.      Mantuano; N.      Silvestris; A.      E. Brunetti; H.      Calvert; A.      Paradiso; A.      Azzariti

Abstract

A large body of evidence point out that the onset of synthetic lethality may provide a useful tool for amplifying the efficacy of drugs in anticancer regimens, to uncover interdependence between genes and to identify predictive factors that would be extremely useful to guide in the selection of more effective targeted drugs and drug combinations for each patient. Here, we provide an overview on the exploitation of synthetic lethality to overcome drug resistance to conventional chemotherapy in several types of solid tumors. We report recent findings on cellular markers and gene mutations which are specifically essential for the viability of cancer cells and for resistance to chemotherapeutics. In addition, new molecularly targeted strategies to overcome drug resistance are suggested.

Keywords: Synthetic lethality, drug resistance, solid tumors, PARP inhibitors, DNA repair pathway, anticancer therapy, anticancer regimens, genes, cellular markers, cancer cells