Can the response to a platinum-based therapy be predicted by the DNA repair status in non-small cell lung cancer?
Preclinical evidence has been accumulating on the impact of the DNA repair status on the sensitivity/resistance to anticancer agents in different tumor types, including lung cancer. The possibility to predict the response to therapy, and specifically to platinum agents, based on tumor specific DNA repair functionality would enable to tailor its use only in those patients with maximum chances to respond, avoiding the burden of toxicity in those ones with lesser chances. We here reviewed the clinical evidence on the prognostic role of DNA repair markers and/or functional assays in predicting the response to a platinum-based chemotherapy in lung cancer patients. Consequently, we focused on those proteins involved in pathways repairing platinum induced DNA inter-strand and intra-strand crosslinks. Most promising clinical trials targeting the nucleotide repair protein ERCC1 in non-small cell lung cancer later on suffered from serious drawbacks. Nevertheless, these results spurred a variety of preclinical studies on a multitude of alternative DNA repair markers. However so far, no one of the analyzed DNA repair markers can be considered a reliable and mature biomarker for selecting patients. We discuss the reasons for such failure which discloses novel strategies for the future.
Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Marianna
M
Macerelli
Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Monica
M
Ganzinelli
Department of Mathematics, University of Athens, Greece.
Cedric
C
Gouedard
Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Massimo
M
Broggini
Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Marina Chiara
MC
Garassino
First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
Helena
H
Linardou
Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Electronic address: giovanna.damia@marionegri.it.
Giovanna
G
Damia
Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
Lisa
L
Wiesmüller
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D004260:DNA Repair; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds
Biomarker; DNA repair; Non-small cell lung cancer; Platinum agents