title: KRAS AND THE REALITY OF PERSONALIZED MEDICINE IN NON-SMALL CELL LUNG CANCER.
abstract: Lung cancer is the leading cause of mortality among all cancer types, worldwide. Latest available global statistics of World Health Organization report 1.59 million casualities in 2012 alone. Worldwide, 1 in 5 cancer deaths are caused by lung cancer. In 2016, in USA alone, estimated new cases of lung cancer are 224,390, of which 158,080 are expected to result in death as reported by National Cancer Institute. Non-small cell lung cancer (NSCLC), a histological subtype, comprises of about 85% of all cases, which is nearly 9 out of 10 lung cancer patients. Efforts are underway to develop and improve targeted therapy strategies. Certain mutations are being clinically targeted such as those inEGFRandALKgenes. However, one of the most frequently mutated genes in NSCLC is theKRASoncogene, which is currently untargetable. Approximately 25% of all types of NSCLC tumors contain KRAS mutations, which remain as an undruggable challenge. These mutations are indicative of poor prognosis and confer negative response to standard chemotherapy. Furthermore, tumors harboringKRASmutations are unlikely to respond to currently available targeted treatments such as Tyrosine Kinase Inhibitors. Therefore, there is a definitive, urgent need to generate new targeted therapy approaches forKRASmutations. Current strategies have major limitations and evolve around targeting molecules upstream and downstream ofKRAS. Direct targeting is not available in the clinic. Combination therapies of multiple agents are being sought. Concentrated efforts are needed to accelerate basic research and consecutive clinical trials to achieve effective targeting ofKRAS.
authors.affiliation: Department of Biological Sciences, Eastern Mediterranean University, Famagusta, North Cyprus, via Mersin-10-Turkey.
authors.forename: Havva O
authors.initials: HO
authors.lastname: Kilgoz
authors.affiliation: Department of Biological Sciences, Eastern Mediterranean University, Famagusta, North Cyprus, via Mersin-10-Turkey.
authors.forename: Guzide
authors.initials: G
authors.lastname: Bender
authors.affiliation: Department of Medicine, Hematology-Oncology, Weill Cornell Medicine, NY, NY, 10065, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Scandura
authors.affiliation: Genomics Core Laboratory, Sloan-Kettering Institute, New York, NY, 10065, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: Department of Biological Sciences, Eastern Mediterranean University, Famagusta, North Cyprus, via Mersin-10-Turkey.|Institute of Public Health Genomics, Department of Genetics & Cell Biology, Research Institutes CAPHRI & GROW, Faculty of Health, Medicine & Life Sciences, Maastricht University, The Netherlands.
authors.forename: Bahar
authors.initials: B
authors.lastname: Taneri
keywords: KRAS; NSCLC; driver mutation; lung cancer; personalized medicine; targeted therapy