Open, phase II randomized trial of gefitinib alone versus olaparib (AZD2281) plus gefitinib in advanced non-small cell lung cancer (NSCLC) patients (P) with epidermal growth factor receptor (EGFR) mutations: Spanish Lung Cancer Group trial (NCT=1513174/GECP-GOAL).

Massutí, Bartomeu; Campelo, Rosario García; Rodríguez-Abreu, Delvys; Remón, Jordi; Majem, Margarita; Galvez, Elisa; Ortega, J.A.; Aparisi, Francisco; Reguart, Noemı́; Sala, María; Isla, Dolores; Ronco, M. Sanchez; Verdu, Ana; Molina-Vila, Miguel Ángel; Casas, Clara Mayo-de las; Pereira, Eva; Cajal, R.; Gonzalez-Arenas, Maria Carmen; Carcereny, Enric; Rosell, Rafael

doi:10.1200/jco.2014.32.15_suppl.tps8127

Cited by 3 publications

(1 citation statement)

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“…For example, an EGFR inhibitor combination has been explored following clinical data from the EURTAC trial showing that low BRCA1 mRNA levels were associated with longer PFS to erlotinib (Tarceva; Genentech) (130). A phase I trial of olaparib with gefitinib (Iressa; AstraZeneca) demonstrated safety and tolerability, as well as promising signals of antitumor activity (131); a phase 2 trial is now accruing (132). Recent pre-clinical data also suggest that inhibition of the receptor tyrosine kinase c-MET hypersensitises cells to PARP inhibition and the clinical evaluation of this finding is likely to follow (133).…”

Section: Combination Strategiesmentioning

confidence: 99%

Targeting DNA Repair in Cancer: Beyond PARP Inhibitors

et al. 2017

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Germline aberrations in critical DNA repair and DNA-damage response (DDR) genes cause cancer predisposition, while various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2 mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell cycle checkpoint activation, trigger apoptosis and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations.

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