Circumventing melanoma chemoresistance by targeting DNA repair.
Available evidence demonstrates that the DNA repair machinery is involved in melanoma resistance to chemotherapeutics. Furhtermore, preclinical findings suggest that interfering with DNA repair could increase chemosensitivity of melanoma cells. However, the clinical implementation of these principles is still in its infancy and no such strategy is currently proven to be effective in patients with advanced melanoma. Since the molecular mechanisms governing the relationship between chemoresistance and DNA repair are not fully elucidated, more basic and translational research is needed to understand the reasons for the failures and to identify novel targets. In this review we summarize the experimental and clinical findings that are fostering the research in this promising field of oncology.
Department Oncological and Surgical Sciences, University of Padova, Italy. simone.mocellin@unipd.it
S
S
Mocellin
L
L
Bertazza
C
C
Benna
P
P
Pilati
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015254:DNA Modification Methylases / Q000378:metabolism; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D015254:DNA Modification Methylases; D011065:Poly(ADP-ribose) Polymerases; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein