Prognostic implications of RAS alterations in diverse malignancies and impact of targeted therapies
| Autor: | David S. Hong, Elizabeth Weihe, Rachel Collier, Razelle Kurzrock, Shumei Kato, Jason K. Sicklick, Aaron M. Goodman, Suzanna Lee, Paul Riviere, Ryosuke Okamura, Theresa J. Whitchurch, Manvita Mareboina, Noor Khalid, Gregory A. Daniels, Scott M. Lippman, Paul T. Fanta |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
MAPK/ERK pathway Male Cancer Research medicine.medical_specialty MAP Kinase Signaling System medicine.medical_treatment Oncology and Carcinogenesis medicine.disease_cause Article California Targeted therapy 03 medical and health sciences 0302 clinical medicine Clinical Research Internal medicine Neoplasms Antineoplastic Combined Chemotherapy Protocols medicine 2.1 Biological and endogenous factors Humans Oncology & Carcinogenesis Molecular Targeted Therapy Precision Medicine Gene Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Cancer Aged Aged 80 and over Mitogen-Activated Protein Kinase Kinases business.industry Cell cycle Middle Aged targeted therapy Prognosis Progression-Free Survival Mapk signaling Observational Studies as Topic 030220 oncology & carcinogenesis Mutation ras Proteins next-generation sequencing Female KRAS business Tyrosine kinase RAS |
| Zdroj: | Int J Cancer International journal of cancer, vol 146, iss 12 |
| Popis: | RAS alterations are often found in difficult-to-treat malignancies and are considered "undruggable." To better understand the clinical correlates and coaltered genes of RAS alterations, we used targeted next-generation sequencing (NGS) to analyze 1,937 patients with diverse cancers. Overall, 20.9% of cancers (405/1,937) harbored RAS alterations. Most RAS-altered cases had genomic coalterations (95.3%, median: 3, range: 0-51), often involving genes implicated in oncogenic signals: PI3K pathway (31.4% of 405 cases), cell cycle (31.1%), tyrosine kinase families (21.5%) and MAPK signaling (18.3%). Patients with RAS-altered versus wild-type RAS malignancies had significantly worse overall survival (OS; p = 0.02 [multivariate]), with KRAS alterations, in particular, showing shorter survival. Moreover, coalterations in both RAS and PI3K signaling or cell-cycle-associated genes correlated with worse OS (p = 0.004 and p |
| Databáze: | OpenAIRE |
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