DGIdb - NRAS Gene Record

NRAS 4893 Clinically ActionableDrug Resistance

Alternate Names:

4893
NRAS PROTO-ONCOGENE, GTPASE
NRAS
ALPS4
CMNS
N-ras
NCMS
NRAS1
NS6
164790
7989
ENSG00000213281
OTTHUMG00000012059
P01111
36
PA31768
GTPase NRas
T35486
KRAS

Gene Info:

Target Class	Miscellaneous
Target Subclass	Miscellaneous
Target Subclass	Hras
Gene Biotype	PROTEIN_CODING

(10 More Sources)

Gene Categories: Category Details

DRUG RESISTANCE
CLINICALLY ACTIONABLE

Publications:

Brammeld et al., 2017, Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations., Genome Res.
Van Cutsem et al., 2015, Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer., J. Clin. Oncol.
Napolitano et al., 2015, Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab., Clin. Cancer Res.
Ciardiello et al., 2016, Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX., Ann. Oncol.
Allegra CJ et al., 2016, Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015., J Clin Oncol
Peeters et al., 2013, Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer., Clin. Cancer Res.
De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.
Douillard et al., 2013, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer., N. Engl. J. Med.
Benson et al., 2017, Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology., J Natl Compr Canc Netw
Gritsman et al., 2014, Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110α., J. Clin. Invest.
Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer
Kiessling et al., 2016, Targeting the mTOR Complex by Everolimus in NRAS Mutant Neuroblastoma., PLoS ONE
Liu et al., 2011, The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway., J. Clin. Endocrinol. Metab.
Posch et al., 2013, Combined targeting of MEK and PI3K/mTOR effector pathways is necessary to effectively inhibit NRAS mutant melanoma in vitro and in vivo., Proc. Natl. Acad. Sci. U.S.A.
Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.
Peeters et al., 2015, Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer., Clin. Cancer Res.
Ho et al., 2013, Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., N. Engl. J. Med.
Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.
Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell
Migliardi et al., 2012, Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomas., Clin. Cancer Res.
Ohashi et al., 2013, Characteristics of lung cancers harboring NRAS mutations., Clin. Cancer Res.
Niessner et al., 2016, PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo., Clin. Cancer Res.
Weisberg et al., 2015, Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies., Leukemia
Falchook et al., 2012, Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial., Lancet Oncol.
Kotschy et al., 2016, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models., Nature
Shen et al., 2016, Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma., Nat. Med.
Kwong et al., 2012, Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma., Nat. Med.
Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature
Zick et al., 2017, Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients., Medicine (Baltimore)
Teh et al., 2016, An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma., Cancer Res.
Vujic et al., 2015, Metformin and trametinib have synergistic effects on cell viability and tumor growth in NRAS mutant cancer., Oncotarget
Long GV et al., 2014, Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma., Nat Commun
Li Y et al., 2011, Genetic variations in multiple drug action pathways and survival in advanced stage non-small cell lung cancer treated with chemotherapy., Clin Cancer Res
Dummer et al., 2017, Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial., Lancet Oncol.
Bendell et al., 2017, A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor., Br. J. Cancer
Morgan et al., 2001, Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling., Blood
Ascierto et al., 2013, MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study., Lancet Oncol.
Vu et al., 2016, Targeting mutant NRAS signaling pathways in melanoma., Pharmacol. Res.
Thumar et al., 2014, MEK targeting in N-RAS mutated metastatic melanoma., Mol. Cancer
Yan J et al., 2018, Analysis of NRAS gain in 657 patients with melanoma and evaluation of its sensitivity to a MEK inhibitor., Eur J Cancer
Garnett et al., 2012, Systematic identification of genomic markers of drug sensitivity in cancer cells., Nature
Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature
Mallon et al., 2011, Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor., Clin. Cancer Res.
Delgado et al., 1992, Differential expression of ras protooncogenes during in vitro differentiation of human erythroleukemia cells., Cancer Res.
Nazarian et al., 2010, Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation., Nature
Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov
Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell
Trunzer et al., 2013, Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma., J. Clin. Oncol.
Girotti et al., 2015, Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma., Cancer Cell
Patnaik et al., 2016, Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors., Cancer Discov
Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer
Milligan et al., 1989, Identification of the pertussis and cholera toxin substrates in normal and N-ras transformed NIH3T3 fibroblasts and an assessment of their involvement in bombesin-stimulation of inositol phospholipid metabolism., Oncogene
Rhyasen et al., 2016, AZD5153: A Novel Bivalent BET Bromodomain Inhibitor Highly Active against Hematologic Malignancies., Mol. Cancer Ther.
Hong et al., 2015, Phase I Dose-Escalation Study of the Multikinase Inhibitor Lenvatinib in Patients with Advanced Solid Tumors and in an Expanded Cohort of Patients with Melanoma., Clin. Cancer Res.
Paraiso et al., 2012, The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms., Clin. Cancer Res.
Lieu et al., 2015, Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts., Oncotarget
Baker et al., 2016, The CDK9 Inhibitor Dinaciclib Exerts Potent Apoptotic and Antitumor Effects in Preclinical Models of MLL-Rearranged Acute Myeloid Leukemia., Cancer Res.
Tsao SC et al., 2015, Monitoring response to therapy in melanoma by quantifying circulating tumour DNA with droplet digital PCR for BRAF and NRAS mutations., Sci Rep

BINIMETINIB NRAS

Interaction Score: 1.02

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BYL719 + MEK162

Indication/Tumor Type acute myeloid leukemia

Response Type sensitive

PMIDs:
24569456 28284557 28152546 28514312 11238126 23414587 27307593 26821351 26987942 24588908 29245078

Sources:
JAX-CKB CIViC OncoKB
AZD-5153 NRAS

Interaction Score: 0.88

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

PMIDs:
27573426

Sources:
JAX-CKB
XL-888 NRAS

Interaction Score: 0.66

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
22351686

Sources:
JAX-CKB
DEL-22379 NRAS

Interaction Score: 0.66

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
26267534

Sources:
JAX-CKB
PANITUMUMAB NRAS

Interaction Score: 0.63

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Approval Status Phase III

PMIDs:
23325582 20619739 24024839 26438111 28275037 26341920

Sources:
JAX-CKB CIViC PharmGKB OncoKB
TRAMETINIB NRAS

Interaction Score: 0.53

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type no benefit

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
22805292 27760111 27500726 22983396 28783719 28514312 26343583 22389471 28179366 27488531 23431193 25504439 25452114 23515407

Sources:
JAX-CKB CIViC PharmGKB
IPILIMUMAB NRAS

Interaction Score: 0.53

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26095797

Sources:
CIViC
OSIMERTINIB NRAS

Interaction Score: 0.53

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB
OBATOCLAX NRAS

Interaction Score: 0.53

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
22460902

Sources:
JAX-CKB
VEMURAFENIB NRAS

Interaction Score: 0.45

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell culture

PMIDs:
21107323 24265153 22389471 26267534 26343583 27523909 23569304

Sources:
JAX-CKB CIViC PharmGKB
LY-3009120 NRAS

Interaction Score: 0.44

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical

Indication/Tumor Type melanoma

Response Type decreased response

PMIDs:
26343583

Sources:
JAX-CKB
PELAREOREP NRAS

Interaction Score: 0.44

Interaction Types & Directionality:

n/a

Interaction Info:

Novel drug target Novel Target

Trial Name Reolysin

PMIDs:
None found

Sources:
TdgClinicalTrial
PLX-4720 NRAS

Interaction Score: 0.44

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell line xenograft

PMIDs:
23431193 25500121

Sources:
JAX-CKB
DABRAFENIB NRAS

Interaction Score: 0.42

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
27523909 22389471 25452114

Sources:
JAX-CKB CIViC PharmGKB
CETUXIMAB NRAS

Interaction Score: 0.4

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + FOLFOX

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

PMIDs:
28179366 25605843 25838391 27002107 26438111 23325582 20619739 24024839 28275037

Sources:
JAX-CKB CIViC PharmGKB OncoKB
E-6201 NRAS

Interaction Score: 0.38

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
23039341

Sources:
JAX-CKB
TAK-733 NRAS

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Approval Status Preclinical - Cell culture

PMIDs:
26439693

Sources:
JAX-CKB
RIBOCICLIB NRAS

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Binimetinib + Ribociclib

Evidence Type Actionable

Approval Status Phase Ib/II

PMIDs:
26987942

Sources:
JAX-CKB CIViC OncoKB
SELUMETINIB NRAS

Interaction Score: 0.3

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Phase I

PMIDs:
23406027 25870145 26343583 22392911 23515407

Sources:
JAX-CKB CIViC OncoKB
DINACICLIB NRAS

Interaction Score: 0.29

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type acute myeloid leukemia

Response Type sensitive

Approval Status Preclinical

PMIDs:
26627013

Sources:
JAX-CKB
PIMASERTIB NRAS

Interaction Score: 0.29

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Everolimus + Pimasertib

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
23629727

Sources:
JAX-CKB
OMIPALISIB NRAS

Interaction Score: 0.28

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type decreased response

Approval Status Preclinical

PMIDs:
23431193 22389471

Sources:
JAX-CKB CIViC
LIFIRAFENIB NRAS

Interaction Score: 0.26

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type predicted – sensitive

Approval Status Phase I

PMIDs:
None found

Sources:
JAX-CKB
AFATINIB NRAS

Interaction Score: 0.26

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB
PD-0325901 NRAS

Interaction Score: 0.24

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type no benefit

Approval Status Preclinical - Cell line xenograft

PMIDs:
27488531

Sources:
JAX-CKB
LENVATINIB NRAS

Interaction Score: 0.22

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Phase I

PMIDs:
26169970

Sources:
JAX-CKB
INOSITOL NRAS

Interaction Score: 0.19

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
2498808

Sources:
NCI
ABEMACICLIB NRAS

Interaction Score: 0.19

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Phase I

PMIDs:
27217383

Sources:
JAX-CKB
MK-2206 NRAS

Interaction Score: 0.15

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid cancer

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
21289267

Sources:
JAX-CKB
SALIRASIB NRAS

Interaction Score: 0.15

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
REGORAFENIB NRAS

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type resistant

Approval Status Preclinical

PMIDs:
23629727 25838391

Sources:
JAX-CKB
ALTEPLASE NRAS

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
1394224

Sources:
NCI
GEDATOLISIB NRAS

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type decreased response

Approval Status Preclinical

PMIDs:
12068308 21325073

Sources:
JAX-CKB
EVEROLIMUS NRAS

Interaction Score: 0.13

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
23629727 26821351

Sources:
JAX-CKB CIViC
PEMBROLIZUMAB NRAS

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pembrolizumab + Trametinib

Indication/Tumor Type melanoma

Response Type no benefit

PMIDs:
28514312

Sources:
JAX-CKB
BUPARLISIB NRAS

Interaction Score: 0.11

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Binimetinib + BKM120

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
27307593

Sources:
JAX-CKB
COBIMETINIB NRAS

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
OncoKB
ADAVOSERTIB NRAS

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
24791855

Sources:
JAX-CKB
PALBOCICLIB NRAS

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
22983396 27488531

Sources:
JAX-CKB
ALPELISIB NRAS

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type sensitive

PMIDs:
24569456

Sources:
JAX-CKB
METFORMIN NRAS

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
25504439

Sources:
CIViC
DACTOLISIB NRAS

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22392911

Sources:
CIViC
GEFITINIB NRAS

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB
CARBOPLATIN NRAS

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
21636554

Sources:
PharmGKB
SORAFENIB NRAS

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pimasertib + Sorafenib

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
23629727

Sources:
JAX-CKB
GEMCITABINE NRAS

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
21636554

Sources:
PharmGKB
CISPLATIN NRAS

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
21636554

Sources:
PharmGKB

Ensembl: ENSG00000213281
- Version: 101_38
Alternate Names:

NRAS Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
TdgClinicalTrial: P01111
- Version: January-2014
Alternate Names:

NRAS Gene Symbol

Gene Info:

Target Class Miscellaneous

Target Subclass Miscellaneous

Target Subclass Hras

Publications:

JAX-CKB: NRAS

Version: 27-September-2017

Alternate Names:

4893 CKB Entrez Id

NRAS CKB Gene Synonym

ALPS4 CKB Gene Synonym

Gene Info:

Publications:

Napolitano et al., 2015, Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab., Clin. Cancer Res.

Ciardiello et al., 2016, Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX., Ann. Oncol.

Brammeld et al., 2017, Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations., Genome Res.

PharmGKB: NRAS

Version: 18-August-2020

Alternate Names:

PA31768 PharmGKB ID

Gene Info:

Publications:

Allegra CJ et al., 2016, Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015., J Clin Oncol

Li Y et al., 2011, Genetic variations in multiple drug action pathways and survival in advanced stage non-small cell lung cancer treated with chemotherapy., Clin Cancer Res

CIViC: NRAS

Version: 14-September-2020

Alternate Names:

4893 Entrez Gene ID

36 CIViC Gene ID

Gene Info:

Gene Categories:

DRUG RESISTANCE, CLINICALLY ACTIONABLE

Publications:

Nazarian et al., 2010, Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation., Nature

Trunzer et al., 2013, Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma., J. Clin. Oncol.

Benson et al., 2017, Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology., J Natl Compr Canc Netw

NCI: NRAS

Version: 14-September-2017

Alternate Names:

Gene Info:

Publications:

Gariglio et al., 1989, Inhibition of interferon-gamma antiviral and antiproliferative activities by ras oncogene expression., J. Natl. Cancer Inst.

Shimada et al., 2003, Genetic susceptibility to thymic lymphomas and K-ras gene mutation in mice after exposure to X-rays and N-ethyl-N-nitrosourea., Int. J. Radiat. Biol.

Delgado et al., 1992, Differential expression of ras protooncogenes during in vitro differentiation of human erythroleukemia cells., Cancer Res.

DoCM: NRAS

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.

Mardis et al., 2009, Recurring mutations found by sequencing an acute myeloid leukemia genome., N. Engl. J. Med.

Irahara et al., 2010, NRAS mutations are rare in colorectal cancer., Diagn. Mol. Pathol.

OncoKB: NRAS
- Version: 23-July-2020
Alternate Names:

4893 OncoKB Entrez Id

CMNS OncoKB Gene Synonym

NS6 OncoKB Gene Synonym

Gene Info:

Publications:
Tempus: NRAS
- Version: 11-November-2018
Alternate Names:

NRAS Gene Symbol

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
TTD: GTPase NRas
- Version: 2020.06.01
Alternate Names:

NRAS TTD Gene Abbreviation

T35486 TTD Target ID

Gene Info:

Publications:
MskImpact: NRAS
- Version: May-2015
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
FoundationOneGenes: NRAS
- Version: 03-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CarisMolecularIntelligence: NRAS
- Version: 04-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
Oncomine: NRAS
- Version: v3
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:

combination therapy	BYL719 + MEK162
Indication/Tumor Type	acute myeloid leukemia
Response Type	sensitive

Evidence Type	Actionable
Approval Status	Preclinical - Cell line xenograft
Response Type	predicted – sensitive

Indication/Tumor Type	melanoma
Response Type	sensitive
Approval Status	Preclinical

Indication/Tumor Type	colorectal cancer
Response Type	predicted – sensitive
Approval Status	Phase III

Response Type	no benefit
Indication/Tumor Type	melanoma
Response Type	sensitive

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	resistant
Approval Status	Preclinical

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Preclinical

combination therapy	Trametinib + Dabrafenib
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	Cetuximab + FOLFOX
Indication/Tumor Type	colorectal cancer
Response Type	predicted – sensitive

combination therapy	Binimetinib + Ribociclib
Evidence Type	Actionable
Approval Status	Phase Ib/II

combination therapy	Everolimus + Pimasertib
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive

Indication/Tumor Type	thyroid cancer
Response Type	sensitive
Approval Status	Preclinical - Cell culture

combination therapy	Pembrolizumab + Trametinib
Indication/Tumor Type	melanoma
Response Type	no benefit

combination therapy	Binimetinib + BKM120
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	Pimasertib + Sorafenib
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive

4893	OncoKB Entrez Id
CMNS	OncoKB Gene Synonym
NS6	OncoKB Gene Synonym

NRAS Gene Record

NRAS 4893 Clinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: n/a

Interaction Info: combination therapy BYL719 + MEK162 Indication/Tumor Type acute myeloid leukemia Response Type sensitive

PMIDs: 24569456 28284557 28152546 28514312 11238126 23414587 27307593 26821351 26987942 24588908 29245078

Sources: JAX-CKB CIViC OncoKB

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell line xenograft Response Type predicted – sensitive

PMIDs: 27573426

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type sensitive Approval Status Preclinical

PMIDs: 22351686

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type sensitive Approval Status Preclinical - Cell culture

PMIDs: 26267534

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type colorectal cancer Response Type predicted – sensitive Approval Status Phase III

PMIDs: 23325582 20619739 24024839 26438111 28275037 26341920

Sources: JAX-CKB CIViC PharmGKB OncoKB

Interaction Types & Directionality: n/a

Interaction Info: Response Type no benefit Indication/Tumor Type melanoma Response Type sensitive

PMIDs: 22805292 27760111 27500726 22983396 28783719 28514312 26343583 22389471 28179366 27488531 23431193 25504439 25452114 23515407

Sources: JAX-CKB CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 26095797

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type resistant Approval Status Preclinical

PMIDs: 25870145

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type Advanced Solid Tumor Response Type sensitive Approval Status Preclinical

PMIDs: 22460902

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type resistant Approval Status Preclinical - Cell culture

PMIDs: 21107323 24265153 22389471 26267534 26343583 27523909 23569304

Sources: JAX-CKB CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: Approval Status Preclinical Indication/Tumor Type melanoma Response Type decreased response

PMIDs: 26343583

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Novel drug target Novel Target Trial Name Reolysin

PMIDs: None found

Sources: TdgClinicalTrial

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type resistant Approval Status Preclinical - Cell line xenograft

PMIDs: 23431193 25500121

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Trametinib + Dabrafenib Indication/Tumor Type melanoma Response Type sensitive

PMIDs: 27523909 22389471 25452114

Sources: JAX-CKB CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Cetuximab + FOLFOX Indication/Tumor Type colorectal cancer Response Type predicted – sensitive

PMIDs: 28179366 25605843 25838391 27002107 26438111 23325582 20619739 24024839 28275037

Sources: JAX-CKB CIViC PharmGKB OncoKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type sensitive Approval Status Preclinical

PMIDs: 23039341

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type colorectal cancer Response Type predicted – sensitive Approval Status Preclinical - Cell culture

PMIDs: 26439693

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Binimetinib + Ribociclib Evidence Type Actionable Approval Status Phase Ib/II

PMIDs: 26987942

Sources: JAX-CKB CIViC OncoKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type resistant Approval Status Phase I

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BYL719 + MEK162

Indication/Tumor Type acute myeloid leukemia

Response Type sensitive

PMIDs:
24569456 28284557 28152546 28514312 11238126 23414587 27307593 26821351 26987942 24588908 29245078

Sources:
JAX-CKB CIViC OncoKB

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

PMIDs:
27573426

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
22351686

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
26267534

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Approval Status Phase III

PMIDs:
23325582 20619739 24024839 26438111 28275037 26341920

Sources:
JAX-CKB CIViC PharmGKB OncoKB

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type no benefit

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
22805292 27760111 27500726 22983396 28783719 28514312 26343583 22389471 28179366 27488531 23431193 25504439 25452114 23515407

Sources:
JAX-CKB CIViC PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
26095797

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
22460902

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell culture

PMIDs:
21107323 24265153 22389471 26267534 26343583 27523909 23569304

Sources:
JAX-CKB CIViC PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical

Indication/Tumor Type melanoma

Response Type decreased response

PMIDs:
26343583

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Novel drug target Novel Target

Trial Name Reolysin

PMIDs:
None found

Sources:
TdgClinicalTrial

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell line xenograft

PMIDs:
23431193 25500121

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
27523909 22389471 25452114

Sources:
JAX-CKB CIViC PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + FOLFOX

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

PMIDs:
28179366 25605843 25838391 27002107 26438111 23325582 20619739 24024839 28275037

Sources:
JAX-CKB CIViC PharmGKB OncoKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

PMIDs:
23039341

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Approval Status Preclinical - Cell culture

PMIDs:
26439693

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Binimetinib + Ribociclib

Evidence Type Actionable

Approval Status Phase Ib/II

PMIDs:
26987942

Sources:
JAX-CKB CIViC OncoKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Phase I

PMIDs:
23406027 25870145 26343583 22392911 23515407

Sources:
JAX-CKB CIViC OncoKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type acute myeloid leukemia

Response Type sensitive

Approval Status Preclinical

PMIDs:
26627013

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a