Base excision repair-mediated resistance to cisplatin in KRAS(G12C) mutant NSCLC cells.

摘要: // Elisa Caiola 1 , Daniela Salles 2 Roberta Frapolli 3 Monica Lupi Giuseppe Rotella 4 Anna Ronchi 5 Marina Chiara Garassino 6 Nikola Mattschas Stefano Colavecchio Massimo Broggini Lisa Wiesmuller Mirko Marabese Laboratory of Molecular Pharmacology, Department Oncology, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy Obstetrics and Gynecology the University Ulm, Germany Cancer Environmental Health Sciences, Centro Nazionale Informazione Tossicologiche, Fondazione Salvatore Maugeri I.R.C.C.S., Pavia, Medical dei Tumori, Correspondence to: Broggini, e-mail: massimo.broggini@marionegri.it Keywords: KRAS, resistance, NSCLC, base excision repair, cisplatin Received: July 21, 2015      Accepted: August 20, Published: September 02, 2015 ABSTRACT KRAS mutations in NSCLC are supposed to indicate a poor prognosis response anticancer treatments but this feature lacks mechanistic basis so far. In tumors, was found be mutated mostly at codons 12 13 pool differing alteration amino acid substitution have been described. The different may differently impact on cancerogenesis drug sensitivity. On basis, we hypothesized that mutational status patients determines profile tumor treatments. paper, isogenic cell clones expressing forms were used determine cisplatin, main clinic against NSCLC. Cells KRAS(G12C) mutation less sensitive treatment both vitro vivo . Systematic analysis uptake, DNA adduct formation damage responses implicated adducts removal revealed might particular because it stimulates Base Excision Repair rapidly remove platinum from even before cross-links. presented results suggest pattern sensitivity/resistance depending these data provide proof principle for further investigations role as predictor response.