Implications of KRAS mutations in acquired resistance to treatment in NSCLC

// Marzia Del Re 1, * , Eleonora Rofi 1, * , Giuliana Restante 1 , Stefania Crucitta 1 , Elena Arrigoni 1 , Stefano Fogli 1 , Massimo Di Maio 2 , Iacopo Petrini 3 and Romano Danesi 1 1 Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy 2 Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Turin, Italy 3 General Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy * These authors contributed equally to this work Correspondence to: Romano Danesi, email: romano.danesi@unipi.it Keywords: KRAS; NSCLC; treatment acquired resistance; TKI; pharmacogenetics Received: September 06, 2017 Accepted: October 27, 2017 Published: December 21, 2017 ABSTRACT Rationale: KRAS is the most common and, simultaneously, the most ambiguous oncogene implicated in human cancer. Despite KRAS mutations were identified in Non Small Cell Lung Cancers (NSCLCs) more than 20 years ago, selective and specific inhibitors aimed at directly abrogating KRAS activity are not yet available. Nevertheless, many therapeutic approaches have been developed potentially useful to treat NSCLC patients mutated for KRAS and refractory to both standard chemotherapy and targeted therapies. The focus of this review will be to provide an overview of the network related to the intricate molecular KRAS pathways, stressing on preclinical and clinical studies that investigate the predictive value of KRAS mutations in NSCLC patients. Materials and Methods: A bibliographic search of the Medline database was conducted for articles published in English, with the keywords KRAS, KRAS mutations in non-small cell lung cancer, KRAS and tumorigenesis, KRAS and TKIs, KRAS and chemotherapy, KRAS and monoclonal antibody, KRAS and immunotherapy, KRAS and drugs, KRAS and drug resistance.