Synthetic lethality to overcome cancer drug resistance.
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.
Clinical Experimental Oncology Laboratory, National Cancer Institute Giovanni Paolo II, Bari, Italy.
L
L
Porcelli
A E
AE
Quatrale
P
P
Mantuano
N
N
Silvestris
A E
AE
Brunetti
H
H
Calvert
A
A
Paradiso
A
A
Azzariti
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D053218:Receptors, Death Domain / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D053218:Receptors, Death Domain; D011065:Poly(ADP-ribose) Polymerases