Prognostic implications of RAS alterations in diverse malignancies and impact of targeted therapies

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% o...

Full description

Saved in:
Bibliographic Details
Published in:International journal of cancer 2020-06, Vol.146 (12), p.3450-3460
Main Authors: Kato, Shumei, Okamura, Ryosuke, Sicklick, Jason K., Daniels, Gregory A., Hong, David S., Goodman, Aaron, Weihe, Elizabeth, Lee, Suzanna, Khalid, Noor, Collier, Rachel, Mareboina, Manvita, Riviere, Paul, Whitchurch, Theresa J., Fanta, Paul T., Lippman, Scott M., Kurzrock, Razelle
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
California - epidemiology
Cancer
Cell cycle
Female
Humans
Male
MAP kinase
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - genetics
Medical research
MEK inhibitors
Middle Aged
Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors
Molecular Targeted Therapy - methods
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - mortality
Neoplasms - pathology
next‐generation sequencing
Observational Studies as Topic
Precision Medicine
Prognosis
Progression-Free Survival
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Protein-tyrosine kinase
RAS
ras Proteins - genetics
ras Proteins - metabolism
Signal transduction
targeted therapy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.32813