KRAS-mutant lung cancers in the era of targeted therapy Journal Article
| Authors: | Naidoo, J.; Drilon, A. |
| Article Title: | KRAS-mutant lung cancers in the era of targeted therapy |
| Abstract: | KRAS-mutant lung cancers account for approximately 25% of non-small cell lung carcinomas, thus representing an enormous burden of cancer worldwide. KRAS mutations are clear drivers of tumor growth and are characterized by a complex biology involving the interaction between mutant KRAS, various growth factor pathways, and tumor suppressor genes. While KRAS mutations are classically associated with a significant smoking history, they are also identified in a substantial proportion of never-smokers. These mutations are found largely in lung adenocarcinomas with solid growth patterns and tumor-infiltrating lymphocytes. A variety of tools are available for diagnosis including Sanger sequencing, multiplex mutational hotspot profiling, and next-generation sequencing. The prognostic and predictive roles of KRAS status remain controversial. It has become increasingly clear, however, that KRAS mutations drive primary resistance to EGFR tyrosine kinase inhibition. Until recently, mutant KRAS was not thought of as a clinically-targetable driver in lung cancers. With the expansion of our knowledge regarding the biology of KRAS-mutant lung cancers and the role of MEK and PBK/mTOR inhibition, the face of targeted therapeutics for this genomic subset of patients is slowly beginning to change. © Springer International Publishing Switzerland 2016. |
| Keywords: | mitogen activated protein kinase; clinical feature; histopathology; sorafenib; erlotinib; placebo; raf protein; cancer combination chemotherapy; drug efficacy; nonhuman; paclitaxel; carboplatin; bortezomib; enzyme inhibition; lung cancer; immunoglobulin enhancer binding protein; mutational analysis; cetuximab; phosphatidylinositol 3 kinase; docetaxel; lung adenocarcinoma; mammalian target of rapamycin; gefitinib; tipifarnib; targeted therapy; ras protein; oncogene k ras; pemetrexed; salirasib; non small cell lung cancer; molecularly targeted therapy; kras mutation; heat shock protein; ridaforolimus; selumetinib; mek inhibition; next generation sequencing; cancer prognosis; trametinib; ganetespib; tivantinib; pf 562271; human; priority journal; article; dactolisib; erlotinib resistance; pi3k inhibition; protein farnesyltransferase; hsp90 inhibition; mtor inhibition; defactinib |
| Journal Title: | Advances in Experimental Medicine and Biology |
| Volume: | 893 |
| ISSN: | 0065-2598 |
| Publisher: | Springer |
| Date Published: | 2016-01-01 |
| Start Page: | 155 |
| End Page: | 178 |
| Language: | English |
| DOI: | 10.1007/978-3-319-24223-1_8 |
| PROVIDER: | scopus |
| PUBMED: | 26667343 |
| DOI/URL: | |
| Notes: | Chapter 8 in "Lung Cancer and Personalized Medicine" (ISBN: 978-3-319-24221-7) -- Article -- Export Date: 7 January 2016 -- Source: Scopus |
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