DGIdb - HRAS Gene Record

HRAS 3265 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

3265
HRAS PROTO-ONCOGENE, GTPASE
HRAS
C-BAS/HAS
C-H-RAS
C-HA-RAS1
CTLO
H-RASIDX
HAMSV
HRAS1
RASH1
p21ras
190020
5173
ENSG00000174775
OTTHUMG00000131919
2822
P01112
BE0001076
2747
PA29444
NM_005343\|NM_176795\|NM_001130442
NP_001123914\|NP_005334\|NP_789765

Gene Info:

Target Class	Miscellaneous
Target Subclass	Miscellaneous
Target Subclass	Hras
Gene Biotype	PROTEIN_CODING
GuideToPharmacology Gene Category Name	RAS subfamily
GuideToPharmacology Gene Category ID	897

(12 More Sources)

Gene Categories: Category Details

TUMOR SUPPRESSOR
KINASE
SERINE THREONINE KINASE
DRUG RESISTANCE
DRUGGABLE GENOME
CLINICALLY ACTIONABLE
ENZYME

Publications:

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.
Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget
Yamaguchi et al., 2016, A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers., Oncotarget
Athuluri-Divakar et al., 2016, A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling., Cell
Koo et al., 1993, Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat., Urol. Res.
Mavrogianni et al., 2002, Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients., Int. J. Hematol.
Hohla et al., 2006, Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel., Proc. Natl. Acad. Sci. U.S.A.
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.
Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature
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
Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene
Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer
Lee et al., 2006, Epidermal growth factor receptor mutations and response to chemotherapy in patients with non-small-cell lung cancer., Jpn. J. Clin. Oncol.
Shepel et al., 1990, Restriction fragment length polymorphisms in the rat N-ras and retinoblastoma genes: their identification and characterization., Oncogene
Kozma et al., 1993, The ras signaling pathway mimics insulin action on glucose transporter translocation., Proc. Natl. Acad. Sci. U.S.A.
Tamano et al., 1996, Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats., Carcinogenesis
Darley et al., 1997, Mutant N-RAS induces erythroid lineage dysplasia in human CD34+ cells., J. Exp. Med.
Jin et al., 2011, Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer., Clin. Cancer Res.
Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer
Ince et al., 2005, Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab., J. Natl. Cancer Inst.
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov
Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov
Soga et al., 1998, Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway., J. Biol. Chem.
Matsui et al., Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor., Oncol. Rep.
Liu et al., 2016, High Sensitivity of an Ha-RAS Transgenic Model of Superficial Bladder Cancer to Metformin Is Associated with ∼240-Fold Higher Drug Concentration in Urine than Serum., Mol. Cancer Ther.
Houlleberghs et al., 2016, Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants., Proc. Natl. Acad. Sci. U.S.A.

LONAFARNIB HRAS

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Measuring inhibition of farnesylation of HRAS by human farnesyltransferase

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

SELUMETINIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung squamous cell carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

SIROLIMUS HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Sirolimus + Trametinib

Indication/Tumor Type head and neck squamous cell carcinoma

Response Type sensitive

Publications:

Yamaguchi et al., 2016, A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers., Oncotarget
RIGOSERTIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Athuluri-Divakar et al., 2016, A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling., Cell
EVEROLIMUS HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type predicted – sensitive

Indication/Tumor Type Advanced Solid Tumor

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget
DASATINIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell line xenograft

Response Type resistant

combination therapy Dasatinib + SCH772984

Publications:

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.
BINIMETINIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type predicted – sensitive

Indication/Tumor Type Advanced Solid Tumor

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget
BUPARLISIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung squamous cell carcinoma

Response Type no benefit

Approval Status Preclinical - Cell culture

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget
MK-2206 HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

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.

TRAMETINIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Sirolimus + Trametinib

Indication/Tumor Type head and neck squamous cell carcinoma

Response Type sensitive

Publications:

Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature

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

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

PANITUMUMAB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Approval Status Preclinical

Publications:

Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene
CI-1040 HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
AZD-8055 HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy AZD8055 + Binimetinib

Indication/Tumor Type lung squamous cell carcinoma

Response Type sensitive

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget
E-6201 HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer
DACTOLISIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Jin et al., 2011, Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer., Clin. Cancer Res.
CABOZANTINIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Phase III

Publications:

Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer

METFORMIN HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Liu et al., 2016, High Sensitivity of an Ha-RAS Transgenic Model of Superficial Bladder Cancer to Metformin Is Associated with ∼240-Fold Higher Drug Concentration in Urine than Serum., Mol. Cancer Ther.

Houlleberghs et al., 2016, Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants., Proc. Natl. Acad. Sci. U.S.A.

CETUXIMAB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Approval Status Preclinical

Publications:

Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene
PELAREOREP HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name Reolysin

Novel drug target Novel Target

Publications:
TIPIFARNIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family Farnesyltransferase inhibitor

Alteration HRAS:.

Publications:
ALPELISIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BYL719 + MEK162

Indication/Tumor Type ovarian cancer

Response Type predicted – sensitive

Publications:
STREPTOZOCIN HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Koo et al., 1993, Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat., Urol. Res.

HYDROXYUREA HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Mavrogianni et al., 2002, Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients., Int. J. Hematol.

DOCETAXEL HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Hohla et al., 2006, Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel., Proc. Natl. Acad. Sci. U.S.A.
GEMCITABINE HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Lee et al., 2006, Epidermal growth factor receptor mutations and response to chemotherapy in patients with non-small-cell lung cancer., Jpn. J. Clin. Oncol.
DIETHYLSTILBESTROL HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Shepel et al., 1990, Restriction fragment length polymorphisms in the rat N-ras and retinoblastoma genes: their identification and characterization., Oncogene
INSULIN HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kozma et al., 1993, The ras signaling pathway mimics insulin action on glucose transporter translocation., Proc. Natl. Acad. Sci. U.S.A.
NITROGLYCERIN HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Tamano et al., 1996, Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats., Carcinogenesis
EPOETIN BETA HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Darley et al., 1997, Mutant N-RAS induces erythroid lineage dysplasia in human CD34+ cells., J. Exp. Med.
BEVACIZUMAB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ince et al., 2005, Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab., J. Natl. Cancer Inst.

TRIFLUOROETHANOL HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

ANTIBIOTIC HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Soga et al., 1998, Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway., J. Biol. Chem.
CHEMBL35482 HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Matsui et al., Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor., Oncol. Rep.

1,6-HEXANEDIOL HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

GUANOSINE TRIPHOSPHATE HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

CHEMBL384759 HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

DABRAFENIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
VEMURAFENIB HRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ensembl: ENSG00000174775
- Version: 101_38
Alternate Names:

HRAS Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
TdgClinicalTrial: P01112
- Version: January-2014
Alternate Names:

HRAS Gene Symbol

Gene Info:

Target Class Miscellaneous

Target Subclass Miscellaneous

Target Subclass Hras

Publications:
GuideToPharmacology: 3265
- Version: 29-September-2020
Alternate Names:

5173 HUGO Gene ID

5173 HUGO Gene Symbol

HRas proto-oncogene, GTPase HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name RAS subfamily

GuideToPharmacology Gene Category ID 897

Gene Categories:

ENZYME

Publications:

JAX-CKB: HRAS

Version: 27-September-2017

Alternate Names:

3265 CKB Entrez Id

HRAS CKB Gene Synonym

C-BAS/HAS CKB Gene Synonym

Gene Info:

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene

CIViC: HRAS

Version: 14-September-2020

Alternate Names:

3265 Entrez Gene ID

2747 CIViC Gene ID

Gene Info:

Gene Categories:

DRUG RESISTANCE

Publications:

Boidot et al., 2016, HRAS G13D, a new mutation implicated in the resistance to anti-EGFR therapies in colorectal cancer, a case report., Int J Colorectal Dis

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

DrugBank: BE0001076

Version: 5.1.7

Alternate Names:

HRAS DrugBank Gene Name

P01112 UniProt Accession

3265 Entrez Gene Id

Gene Info:

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

NCI: HRAS

Version: 14-September-2017

Alternate Names:

Gene Info:

Publications:

Tamano et al., 1996, Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats., Carcinogenesis

Soga et al., 1998, Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway., J. Biol. Chem.

Matsui et al., Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor., Oncol. Rep.

HingoraniCasas: ENSG00000174775
- Version: 31-May-2017
Alternate Names:

ENSG00000174775 Gene Symbol

HRAS Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
OncoKB: HRAS
- Version: 23-July-2020
Alternate Names:

3265 OncoKB Entrez Id

C-H-RAS OncoKB Gene Synonym

HAMSV OncoKB Gene Synonym

Gene Info:

Publications:
PharmGKB: HRAS
- Version: 18-August-2020
Alternate Names:

PA29444 PharmGKB ID

Gene Info:

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

HRAS Gene Symbol

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CGI: HRAS
- Version: 27-September-2017
Alternate Names:

Gene Info:

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:

Details of the Assay for Interaction	Measuring inhibition of farnesylation of HRAS by human farnesyltransferase
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Indication/Tumor Type	lung squamous cell carcinoma
Response Type	sensitive
Approval Status	Preclinical - Cell line xenograft

combination therapy	Sirolimus + Trametinib
Indication/Tumor Type	head and neck squamous cell carcinoma
Response Type	sensitive

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Preclinical - Cell culture

Indication/Tumor Type	urinary bladder cancer
Response Type	predicted – sensitive
Indication/Tumor Type	Advanced Solid Tumor

Evidence Type	Actionable
Approval Status	Preclinical - Cell culture
Response Type	sensitive

Indication/Tumor Type	melanoma
Response Type	sensitive
Approval Status	Preclinical

combination therapy	AZD8055 + Binimetinib
Indication/Tumor Type	lung squamous cell carcinoma
Response Type	sensitive

Indication/Tumor Type	thyroid cancer
Response Type	sensitive
Approval Status	Preclinical

Indication/Tumor Type	thyroid medullary carcinoma
Response Type	sensitive
Approval Status	Phase III

combination therapy	BYL719 + MEK162
Indication/Tumor Type	ovarian cancer
Response Type	predicted – sensitive

5173	HUGO Gene ID
5173	HUGO Gene Symbol
HRas proto-oncogene, GTPase	HUGO Gene Name

3265	CKB Entrez Id
HRAS	CKB Gene Synonym
C-BAS/HAS	CKB Gene Synonym

HRAS	DrugBank Gene Name
P01112	UniProt Accession
3265	Entrez Gene Id

3265	OncoKB Entrez Id
C-H-RAS	OncoKB Gene Synonym
HAMSV	OncoKB Gene Synonym

HRAS Gene Record

HRAS 3265 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction Measuring inhibition of farnesylation of HRAS by human farnesyltransferase Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications:

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung squamous cell carcinoma Response Type sensitive Approval Status Preclinical - Cell line xenograft

Publications: Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther. Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Sirolimus + Trametinib Indication/Tumor Type head and neck squamous cell carcinoma Response Type sensitive

Publications: Yamaguchi et al., 2016, A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers., Oncotarget

Interaction Types & Directionality: n/a

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

Publications: Athuluri-Divakar et al., 2016, A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling., Cell

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type urinary bladder cancer Response Type predicted – sensitive Indication/Tumor Type Advanced Solid Tumor

Publications: Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality: n/a

Interaction Info: Approval Status Preclinical - Cell line xenograft Response Type resistant combination therapy Dasatinib + SCH772984

Publications: Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type urinary bladder cancer Response Type predicted – sensitive Indication/Tumor Type Advanced Solid Tumor

Publications: Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung squamous cell carcinoma Response Type no benefit Approval Status Preclinical - Cell culture

Publications: Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell culture Response Type sensitive

Publications: 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.

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Sirolimus + Trametinib Indication/Tumor Type head and neck squamous cell carcinoma Response Type sensitive

Interaction Types & Directionality: n/a

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

Publications: Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene

Interaction Types & Directionality: n/a

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

Publications: Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell

Interaction Types & Directionality: n/a

Interaction Info: combination therapy AZD8055 + Binimetinib Indication/Tumor Type lung squamous cell carcinoma Response Type sensitive

Publications: Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality: n/a

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

Publications: Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer

Interaction Types & Directionality: n/a

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

Publications: Jin et al., 2011, Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer., Clin. Cancer Res.

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type thyroid medullary carcinoma Response Type sensitive Approval Status Phase III

Publications: Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type urinary bladder cancer Response Type sensitive Approval Status Preclinical

Interaction Types & Directionality: n/a

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

Publications: Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene

Interaction Types & Directionality: n/a

Interaction Info: Trial Name Reolysin Novel drug target Novel Target

Publications:

Interaction Types & Directionality: n/a

Interaction Info: Drug family Farnesyltransferase inhibitor Alteration HRAS:.

Publications:

Interaction Types & Directionality: n/a

Interaction Info: combination therapy BYL719 + MEK162 Indication/Tumor Type ovarian cancer Response Type predicted – sensitive

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

Publications: Koo et al., 1993, Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat., Urol. Res.

Interaction Types & Directionality: n/a

Interaction Info:

Publications: Mavrogianni et al., 2002, Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients., Int. J. Hematol.

Interaction Types & Directionality: n/a

Interaction Info:

Publications: Hohla et al., 2006, Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel., Proc. Natl. Acad. Sci. U.S.A.

Interaction Types & Directionality: n/a

Interaction Info:

Publications: Lee et al., 2006, Epidermal growth factor receptor mutations and response to chemotherapy in patients with non-small-cell lung cancer., Jpn. J. Clin. Oncol.

Interaction Types & Directionality: n/a

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Measuring inhibition of farnesylation of HRAS by human farnesyltransferase

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung squamous cell carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Sirolimus + Trametinib

Indication/Tumor Type head and neck squamous cell carcinoma

Response Type sensitive

Publications:

Yamaguchi et al., 2016, A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Athuluri-Divakar et al., 2016, A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling., Cell

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type predicted – sensitive

Indication/Tumor Type Advanced Solid Tumor

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell line xenograft

Response Type resistant

combination therapy Dasatinib + SCH772984

Publications:

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type predicted – sensitive

Indication/Tumor Type Advanced Solid Tumor

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung squamous cell carcinoma

Response Type no benefit

Approval Status Preclinical - Cell culture

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

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.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Sirolimus + Trametinib

Indication/Tumor Type head and neck squamous cell carcinoma

Response Type sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Approval Status Preclinical

Publications:

Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy AZD8055 + Binimetinib

Indication/Tumor Type lung squamous cell carcinoma

Response Type sensitive

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Jin et al., 2011, Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer., Clin. Cancer Res.

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Phase III

Publications:

Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type sensitive

Approval Status Preclinical

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Approval Status Preclinical

Publications:

Kasper et al., 2013, Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade., Oncogene

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name Reolysin

Novel drug target Novel Target

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family Farnesyltransferase inhibitor

Alteration HRAS:.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BYL719 + MEK162

Indication/Tumor Type ovarian cancer

Response Type predicted – sensitive

Interaction Types & Directionality:

n/a

Publications:

Koo et al., 1993, Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat., Urol. Res.

Interaction Types & Directionality:

n/a

Publications:

Mavrogianni et al., 2002, Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients., Int. J. Hematol.

Interaction Types & Directionality:

n/a

Publications:

Hohla et al., 2006, Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel., Proc. Natl. Acad. Sci. U.S.A.

Interaction Types & Directionality:

n/a

Publications:

Lee et al., 2006, Epidermal growth factor receptor mutations and response to chemotherapy in patients with non-small-cell lung cancer., Jpn. J. Clin. Oncol.

Interaction Types & Directionality:

n/a

Publications:

Shepel et al., 1990, Restriction fragment length polymorphisms in the rat N-ras and retinoblastoma genes: their identification and characterization., Oncogene

Interaction Types & Directionality:

n/a

Publications:

Kozma et al., 1993, The ras signaling pathway mimics insulin action on glucose transporter translocation., Proc. Natl. Acad. Sci. U.S.A.

Interaction Types & Directionality:

n/a

Publications:

Tamano et al., 1996, Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats., Carcinogenesis

Interaction Types & Directionality:

n/a

Publications:

Darley et al., 1997, Mutant N-RAS induces erythroid lineage dysplasia in human CD34+ cells., J. Exp. Med.

Interaction Types & Directionality:

n/a

Publications:

Ince et al., 2005, Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab., J. Natl. Cancer Inst.

Interaction Types & Directionality:

n/a

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Interaction Types & Directionality:

n/a

Publications:

Soga et al., 1998, Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway., J. Biol. Chem.

Interaction Types & Directionality:

n/a