TY - JOUR
T1 - Can the response to a platinum-based therapy be predicted by the DNA repair status in non-small cell lung cancer?
AU - Macerelli, Marianna
AU - Ganzinelli, Monica
AU - Gouedard, Cedric
AU - Broggini, Massimo
AU - Garassino, Marina Chiara
AU - Linardou, Helena
AU - Damia, Giovanna
AU - Wiesmüller, Lisa
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - DNA repair
KW - Non-small cell lung cancer
KW - Platinum agents
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U2 - 10.1016/j.ctrv.2016.05.004
DO - 10.1016/j.ctrv.2016.05.004
M3 - Review article
VL - 48
SP - 8
EP - 19
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
SN - 0305-7372
ER -