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Gene Symbol HRAS
Synonyms C-BAS/HAS | C-H-RAS | C-HA-RAS1 | CTLO | H-RASIDX | HAMSV | HRAS1 | p21ras | RASH1
Gene Description HRAS, HRas proto-oncogene, GTPase, is a member of the small GTPase family that upon activation by growth factors stimulates multiple downstream pathways such as RAF and PI3K to promote cell proliferation and survival (PMID: 21779504, PMID: 32241873). HRAS activating mutations are commonly found in tumors, including dermatological, head and neck, thyroid, kidney, bladder cancers (PMID: 29524560), squamous cell papilloma (PMID: 31960612), and breast adenomyoepitheliomas (PMID: 31887226).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
3265 11 11p15.5 NM_005343 Oncogene (PMID: 30606230)

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
HRAS wild-type melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with wild-type HRAS (PMID: 23039341). 23039341
HRAS wild-type cancer predicted - sensitive FTI-277 Preclinical Actionable In a preclinical study, the farnesyltransferase inhibitor FTI-277 sensitized Hras transformed rat fibroblasts to radiation therapy (PMID: 8620483). 8620483
HRAS mutant endometrial cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human endometrial cancer cells harboring mutant HRAS in culture (PMID: 26343583). 26343583
HRAS mutant transitional cell carcinoma resistant Trametinib Preclinical Actionable In a preclinical study, human urinary transitional cell carcinoma cells harboring mutant HRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
HRAS mutant Advanced Solid Tumor predicted - sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, human solid tumor cell lines harboring HRAS mutations demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) in culture compared to cell lines with wild-type HRAS (PMID: 26544513). 26544513
HRAS mutant Advanced Solid Tumor predicted - sensitive Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) inhibited growth and induced apoptosis in human solid tumor cell lines harboring HRAS mutations in culture (PMID: 26544513). 26544513
HRAS mutant Advanced Solid Tumor predicted - sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, human solid tumor cell lines harboring HRAS mutations demonstrated increased sensitivity to growth inhibition by Selumetinib (AZD6244) in culture compared to cell lines with wild-type HRAS (PMID: 26544513). 26544513
HRAS mutant transitional cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS missense (Q61R, G12S, G13R) or frameshift (V29Cfs*19) mutations, progression-free survival was significantly improved in patients harboring HRAS mutations (5.1 vs 0.8 months, HR=0.262) compared to wild-type patients (PMID: 32636318; NCT02535650). 32636318
HRAS mutant head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (AIM-HN), Zarnestra (tipifarnib) demonstrated safety and preliminary activity in patients with recurrent or metastatic head and neck squamous cell carcinoma harboring mutations in HRAS, resulting in an objective response rate of 20% (10/50, 1 complete and 9 partial responses), disease control rate of 48% (24/50), with stable disease in 14 patients, median progression-free survival of 2.6 mo, and median overall survival of 7 mo (Ann Oncol (2023) 34 (suppl_2): S1286-S1287; NCT03719690). detail...
HRAS mutant head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (KO-TIP-001), Zarnestra (tipifarnib) treatment resulted in an objective response rate of 55% (11/20) in patients with head and neck squamous cell carcinoma harboring HRAS missense mutations at a variant allele frequency over 20%, with nine patients achieved stable disease and a median progression-free survival of 5.6 months (PMID: 33750196; NCT02383927). 33750196
HRAS mutant head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cell lines harboring an HRAS mutation were sensitive to treatment with Zarnestra (tipifarnib), demonstrating reduced cell growth and decreased phosphorylation of Erk and Mek, and inhibition of spheroid viability in culture (PMID: 32727882). 32727882
HRAS mutant salivary gland cancer predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (KO-TIP-001), Zarnestra (tipifarnib) treatment resulted in an objective response rate of 8% (1/12) in patients with recurrent or metastatic salivary gland cancer harboring HRAS mutations, with a median progression-free survival of 7 months (J Clin Oncol 38: 2020 (suppl; abstr 6504); NCT02383927). detail...
HRAS mutant medullary thyroid carcinoma sensitive Cabozantinib Guideline Actionable Cometriq (cabozantinib) is included in guidelines for patients with advanced or metastatic medullary thyroid carcinoma harboring RAS mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 35491008 31549998 detail...
HRAS mutant medullary thyroid carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression-free survival (47 vs 8 weeks, HR 0.15, p=0.0317) compared to placebo in thyroid medullary carcinoma patients harboring RAS mutations (PMID: 27525386). 27525386
HRAS mutant urinary bladder cancer sensitive Metformin Preclinical Actionable In a preclinical study, mouse models of bladder cancer harboring an HRAS mutation were sensitive to Glucophage (metformin), resulting in tumor growth reduction and prevention of hyperplasia regression (PMID: 26921394). 26921394
HRAS mutant ovarian cancer predicted - sensitive Alpelisib + Binimetinib Phase Ib/II Actionable In a Phase Ib study, Alpelisib (BYL719) in combination with Binimetinib (MEK162) demonstrated preliminary safety and efficacy in patients with RAS-mutant advanced solid tumors, including patients with ovarian cancer (J Clin Oncol 32:5s, 2014 (suppl; abstr 9051). detail...
HRAS mutant breast cancer decreased response PI-273 Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines harboring RAS mutations, including HRAS-mutant cell lines, demonstrated decreased sensitivity to growth inhibition by PI-273, in culture (PMID: 28827373). 28827373
HRAS mut PIK3CA R88Q high grade glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in growth inhibition of astrocytoma cells with an HRAS mutation and expressing PIK3CA R88Q in culture, but at a higher drug concentration compared to cells without mutant HRAS (PMID: 29975751). 29975751
HRAS mut PIK3CA E542K high grade glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in growth inhibition of astrocytoma cells with an HRAS mutation expressing PIK3CA E542K in culture, but at a higher drug concentration compared to cells without mutant HRAS (PMID: 29975751). 29975751
HRAS mut PIK3CA M1043V high grade glioma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Buparlisib (BKM120) and Koselugo (selumetinib) led to a synergistic effect, resulting in growth inhibition of astrocytoma cells with an HRAS mutation and expressing PIK3CA M1043V in culture, but at a higher drug concentration compared to cells without mutant HRAS (PMID: 29975751). 29975751
HRAS Q61K rhabdomyosarcoma no benefit Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and viability in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture, but did not inhibit ERK signaling in cell line xenograft models and led to tumor progression (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma not predictive Rigosertib Preclinical - Cell culture Actionable In a preclinical study, Rigosertib (ON01910) inhibited cell viability and induced apoptosis and cell cycle arrest in rhabdomyosarcoma cells harboring HRAS Q61K in culture, however, cells with wild-type HRAS demonstrated the same response, and mechanistically, the response was found to be due to Rigosertib (ON0190) binding to tubulin (PMID: 33158997). 33158997
HRAS Q61K rhabdomyosarcoma sensitive LY3009120 + LY3214996 Preclinical - Cell line xenograft Actionable In a preclinical study, LY3214996 and LY3009120 combination treatment synergistically induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture and induced tumor growth regression in a xenograft model (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma sensitive LY3009120 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and LY3009120 combination treatment synergistically inhibited Erk phosphorylation, proliferation, and colony formation and induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma sensitive LY3214996 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and LY3214996 combination treatment synergistically inhibited growth and induced apoptosis and cell cycle arrest in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture and induced tumor regression in a xenograft model (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) synergistically inhibited growth of rhabdomyosarcoma cell lines harboring HRAS Q61K in culture, and resulted in tumor regression and increased survival compared to either treatment alone in a cell line xenograft model (PMID: 36322002). 36322002
BRAF G466E HRAS Q61K melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF G466E and HRAS Q61K in culture (PMID: 28783719). 28783719
HRAS Q61K PTEN dec exp rhabdomyosarcoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, decreasing Pten expression through shRNA knockdown in a rhabdomyosarcoma cell line harboring HRAS Q61K conferred resistance to Mekinist (trametinib) treatment in culture (PMID: 36322002). 36322002
HRAS Q61K PTEN dec exp rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Ganitumab (AMG-479) sensitized a rhabdomyosarcoma cell line harboring HRAS Q61K with low PTEN expression to treatment with Mekinist (trametinib), resulting in reduced cell growth in culture (PMID: 36322002). 36322002
HRAS G12S head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a clinical case study, Zarnestra (tipifarnib) treatment resulted in a partial response that lasted for 8 months in a patient with ear canal squamous cell carcinoma harboring HRAS G12S (PMID: 38219706). 38219706
HRAS G12S head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Pdx Actionable In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS G12S was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). 32727882
HRAS G12S renal pelvis transitional cell carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with renal pelvis transitional cell carcinoma harboring HRAS G12S achieved a partial response (PMID: 32636318; NCT02535650). 32636318
HRAS G12S lung squamous cell carcinoma sensitive Buparlisib + Carboplatin + Paclitaxel Preclinical - Pdx Actionable In a preclinical study, the addition of Buparlisib (BKM120) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558). 39199558
HRAS G12S head and neck squamous cell carcinoma sensitive Alpelisib + Tipifarnib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Piqray (alpelisib) and Zarnestra (tipifarnib) resulted in enhanced tumor growth inhibition compared to monotherapy in a patient-derived xenograft (PDX) model of head and neck squamous cell carcinoma harboring HRAS G12S (PMID: 38219706). 38219706
HRAS G12S lung squamous cell carcinoma sensitive Cisplatin + Pemetrexed Disodium + Trametinib Preclinical - Pdx Actionable In a preclinical study, the addition of Mekinist (trametinib) to treament with the combination of Alimta (pemetrexed disodium) and Platinol (cisplatin) resulted in improved tumor growth inhibition compared to chemotherapy or Mekinist (trametinib) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558). 39199558
HRAS G12V Advanced Solid Tumor resistant Cetuximab Preclinical Actionable In a preclinical study, tumor cells expressing HRAS G12V demonstrated resistance to treatment with Erbitux (cetuximab) (PMID: 22797062). 22797062
HRAS G12V melanoma sensitive CI-1040 Preclinical Actionable In a preclinical study CI-1040 (PD-184352) inhibited melanoma progression in a transgenic zebrafish model of melanoma expressing HRAS G12V (PMID: 26267534). 26267534
HRAS G12V Advanced Solid Tumor sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing HRAS G12V demonstrated sensitivity to growth inhibition by Afinitor (everolimus) in culture (PMID: 26544513). 26544513
HRAS G12V Advanced Solid Tumor sensitive Binimetinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing HRAS G12V demonstrated sensitivity to growth inhibition by Binimetinib (MEK162) in culture (PMID: 26544513). 26544513
HRAS G12V Advanced Solid Tumor resistant Panitumumab Preclinical Actionable In a preclinical study, tumor cells expressing HRAS G12V demonstrated resistance to treatment with Vectibix (panitumumab) (PMID: 22797062). 22797062
HRAS G12V urinary bladder cancer sensitive RAF265 Preclinical - Cell culture Actionable In a preclinical study, RAF265 treatment decreased viability and colony formation of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34554931). 34554931
HRAS G12V high grade glioma sensitive SF1126 Preclinical - Cell line xenograft Actionable In a preclinical study, SF1126 inhibited Akt activation, proliferation, and migration of transgenic mouse glioma cells expressing HRAS G12V in culture, and suppressed tumor growth in xenograft models (PMID: 25425962). 25425962
HRAS G12V head and neck squamous cell carcinoma sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, Zarnestra (tipifarnib) treatment led to decreased cell viability and inhibition of clonogenic and anchorage-independent growth in a head and neck squamous cell carcinoma cell line harboring HRAS G12V in culture (PMID: 35247914). 35247914
HRAS G12V Advanced Solid Tumor sensitive Rigosertib Sodium Preclinical - Cell culture Actionable In a preclinical study, Rigosertib (ON 01910.Na) inhibited oncogenic transformation in fibroblast cells over-expressing HRAS G12V in culture (PMID: 27104980). 27104980
HRAS G12V Advanced Solid Tumor sensitive Pz-1 Preclinical - Cell line xenograft Actionable In a preclinical study, Pz-1 reduced tumor growth in xenograft models of transformed cells over expressing HRAS G12V in a dose-dependent manner (PMID: 26126987). 26126987
HRAS G12V urinary bladder cancer sensitive LXH 254 Preclinical - Cell culture Actionable In a preclinical study, LXH 254 treatment decreased viability of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34554931). 34554931
HRAS G12V urinary bladder cancer sensitive Everolimus + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Selumetinib (AZD6244) and Afinitor (everolimus) reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 26544513). 26544513
HRAS G12V urinary bladder cancer sensitive Binimetinib + Everolimus Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a bladder cell line harboring HRAS G12V in culture (PMID: 26544513). 26544513
HRAS G12V Advanced Solid Tumor sensitive Binimetinib + Everolimus Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) worked synergistically to inhibit growth of transformed cells expressing HRAS G12V in culture (PMID: 26544513). 26544513
HRAS G12V Advanced Solid Tumor predicted - sensitive SR9009 Preclinical - Cell culture Actionable In a preclinical study, SR9009 treatment resulted in apoptosis in HRAS G12V-induced senescent firbroblast cells in culture (PMID: 29320480). 29320480
HRAS G12V Advanced Solid Tumor predicted - sensitive SR9011 Preclinical - Cell culture Actionable In a preclinical study, SR9011 treatment resulted in apoptosis in HRAS G12V-induced senescent firbroblast cells in culture (PMID: 29320480). 29320480
HRAS G12V urinary bladder cancer sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34337566). 34337566
HRAS G12V Advanced Solid Tumor sensitive WM-8014 Preclinical Actionable In a preclinical study, WM-8014 inhibited proliferation of a transformed mouse cell line expressing HRAS G12V in culture, and inhibited proliferation and induced senescence in a transgenic zebrafish model (PMID: 30069049). 30069049
HRAS G12V head and neck squamous cell carcinoma predicted - sensitive Alpelisib + Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, the addition of Piqray (alpelisib) sensitized head and neck squamous cell carcinoma cell lines harboring HRAS G12V to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and apoptosis in culture (PMID: 35247914). 35247914
HRAS G12V urinary bladder cancer sensitive RAF265 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, RAF265 and Mekinist (trametinib) combination treatment inhibited colony formation compared to RAF265 alone in cultured cells harboring HRAS G12V (PMID: 34554931). 34554931
FGFR3 dec exp FGFR3 wild-type HRAS G12V transitional cell carcinoma resistant Fexagratinib Preclinical Actionable In a preclinical study, urothelial cancer cells with low expression of wild-type FGFR3 that harbored HRAS G12V demonstrated resistance to AZD4547 in culture (PMID: 22869148). 22869148
FGFR3 dec exp FGFR3 wild-type HRAS G12V transitional cell carcinoma resistant PD173074 Preclinical Actionable In a preclinical study, urothelial cancer cells with low expression of wild-type FGFR3 that harbored HRAS G12V demonstrated resistance to PD173074 in culture (PMID: 22869148). 22869148
FGFR3 dec exp FGFR3 wild-type HRAS G12V transitional cell carcinoma decreased response AZ8010 Preclinical Actionable In a preclinical study, urothelial cancer cells with low expression of wild-type FGFR3 that harbored HRAS G12V demonstrated resistance to AZ8010 in culture (PMID: 22869148). 22869148
HRAS G12V HRAS R135A Advanced Solid Tumor resistant NS1 Preclinical Actionable In a preclinical study, introducing HRAS R135A mutation in transformed cells expressing HRAS G12V resulted in reduced binding of Hras to NS1, leading to resistance to Mapk pathway inhibition in cell culture (PMID: 27820802). 27820802
HRAS G12V HRAS R135K Advanced Solid Tumor resistant NS1 Preclinical Actionable In a preclinical study, introducing HRAS R135K mutation in transformed cells expressing HRAS G12V resulted in reduced binding of Hras to NS1, leading to resistance to Mapk pathway inhibition in cell culture (PMID: 27820802). 27820802
HRAS inact mut thyroid cancer sensitive Dactolisib Preclinical Actionable In a preclinical study, BEZ235 inhibited growth of thyroid cancer cells harboring an HRAS pathway activating mutation in cell culture (PMID: 21831957). 21831957
HRAS A59T RET A883F RET A883T medullary thyroid carcinoma predicted - resistant Pralsetinib Case Reports/Case Series Actionable In a retrospective analysis, a medullary thyroid carcinoma patient harboring RET A883T progressed on treatment with Gavreto (pralsetinib) and was found to have acquired RET A883F and HRAS A59T (PMID: 38127829; NCT03157128, NCT03037385, NCT03780517). 38127829
HRAS G12C head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Cell line xenograft Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line xenograft model harboring HRAS G12C was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth and vessel formation, increased apoptotic activity, and decreased cell proliferation (PMID: 32727882). 32727882
HRAS G12C Advanced Solid Tumor sensitive Sotorasib Preclinical - Cell culture Actionable In a preclinical study, Lumakras (sotorasib) inhibited viability of cultured cells expressing HRAS G12C (PMID: 38236605). 38236605
HRAS G12C Advanced Solid Tumor sensitive JDQ443 Preclinical - Cell culture Actionable In a preclinical study, JDQ443 inhibited viability of cultured cells expressing HRAS G12C (PMID: 38236605). 38236605
HRAS G12C Advanced Solid Tumor sensitive RM-018 Preclinical - Cell culture Actionable In a preclinical study, RM-018 inhibited viability of cultured cells expressing HRAS G12C (PMID: 38236605). 38236605
HRAS G12D head and neck squamous cell carcinoma sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, Zarnestra (tipifarnib) treatment led to decreased cell viability and inhibition of clonogenic and anchorage-independent growth in head and neck squamous cell carcinoma cell lines harboring HRAS G12D in culture (PMID: 35247914). 35247914
HRAS G12D head and neck squamous cell carcinoma sensitive Alpelisib + Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, the addition of Piqray (alpelisib) sensitized head and neck squamous cell carcinoma cell lines harboring HRAS G12D to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). 35247914
HRAS G12D Advanced Solid Tumor no benefit MRTX-1133 Preclinical - Cell culture Actionable In a preclinical study, cultured cells expressing HRAS G12D were not sensitive to treatment with MRTX1133 (PMID: 37339170). 37339170
HRAS G12D head and neck squamous cell carcinoma sensitive SCH772984 + Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, the addition of SCH772984 sensitized head and neck squamous cell carcinoma cell lines harboring HRAS G12D to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). 35247914
HRAS G12D head and neck squamous cell carcinoma sensitive Tipifarnib + Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, combination treatment with Ulixertinib (BVD-523) and Zarnestra (tipifarnib) resulted in a synergistic effect, with enhanced apoptosis in a head and neck squamous cell carcinoma cell lines harboring HRAS G12D in culture (PMID: 35247914). 35247914
HRAS G12D HRAS Q95H Advanced Solid Tumor sensitive MRTX-1133 Preclinical - Cell culture Actionable In a preclinical study, cultured cells expressing HRAS G12D and HRAS Q95H were sensitive to treatment with MRTX1133, demonstrating decreased cell viability (PMID: 37339170). 37339170
HRAS G13R thyroid cancer sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). 27222538
HRAS G13R thyroid cancer sensitive MK2206 Preclinical - Cell culture Actionable In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring HRAS G13R (PMID: 21289267). 21289267
HRAS G13R thyroid cancer sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) inhibited growth of a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). 27222538
HRAS G13R head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Pdx Actionable In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS G13R was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). 32727882
HRAS G13R renal pelvis transitional cell carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with renal pelvis transitional cell carcinoma harboring HRAS G13R achieved a partial response (PMID: 32636318; NCT02535650). 32636318
HRAS G13R Advanced Solid Tumor sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, expression of HRAS G13R in an HRAS-null, NRAS-null, and KRAS knockout cell line conferred sensitivity to Zarnestra (tipifarnib) in culture, resulting in decreased cell viability (PMID: 39152269). 39152269
HRAS G13R thyroid cancer sensitive Dasatinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited growth and induced apoptosis in a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). 27222538
HRAS G13R thyroid cancer sensitive Dasatinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Koselugo (selumetinib) synergistically inhibited growth and induced apoptosis in a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). 27222538
HRAS G13R rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment resulted in tumor regression and increased progression-free survival in a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring HRAS G13R (PMID: 36322002). 36322002
HRAS G13R Advanced Solid Tumor sensitive Tipifarnib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination treatment with Zarnestra (tipifarnib) and Mekinist (trametinib) decreased viability of HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R compared to Zarnestra (tipifarnib) treatment alone in culture (PMID: 39152269). 39152269
HRAS G13R PIK3CA H1047R Advanced Solid Tumor resistant Alpelisib Preclinical - Cell culture Actionable In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and PIK3CA H1047R were resistant to Piqray (alpelisib) in culture (PMID: 39152269). 39152269
HRAS G13R PIK3CA H1047R Advanced Solid Tumor resistant Pictilisib Preclinical - Cell culture Actionable In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and PIK3CA H1047R were resistant to Pictilisib (GDC-0941) in culture (PMID: 39152269). 39152269
HRAS G13R PIK3CA H1047R Advanced Solid Tumor resistant Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and PIK3CA H1047R were resistant to Zarnestra (tipifarnib) in culture (PMID: 39152269). 39152269
ALK F1245Y HRAS G13R neuroblastoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a neuroblastoma patient harboring ALK F1245Y developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired HRAS G13R via circulating tumor DNA (PMID: 37147298; NCT03107988). 37147298
BRAF G466E HRAS G13R Advanced Solid Tumor sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and BRAF G466E were sensitive to Mekinist (trametinib) in culture, demonstrating decreased cell viability (PMID: 39152269). 39152269
BRAF G466E HRAS G13R Advanced Solid Tumor sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and BRAF G466E were sensitive to Zarnestra (tipifarnib) in culture, demonstrating decreased cell viability (PMID: 39152269). 39152269
BRAF G466E HRAS G13R Advanced Solid Tumor sensitive Tipifarnib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination treatment with Zarnestra (tipifarnib) and Mekinist (trametinib) resulted in decreased viability of HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and BRAF G466E in culture (PMID: 39152269). 39152269
HRAS G13R PTEN loss Advanced Solid Tumor resistant Pictilisib Preclinical - Cell culture Actionable In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells with PTEN loss and expressing HRAS G13R were not sensitive to treatment with Pictilisib (GDC-0941) in culture (PMID: 39152269). 39152269
HRAS G13R PTEN loss Advanced Solid Tumor resistant AZD8186 Preclinical - Cell culture Actionable In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells with PTEN loss and expressing HRAS G13R were not sensitive to treatment with AZD8186 in culture (PMID: 39152269). 39152269
HRAS G13V PIK3CA E545K salivary gland carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a clinical case study, Zarnestra (tipifarnib) treatment resulted in a partial response and progression-free survival lasting more than 5 months in a patient with androgen-receptor (AR)-positive salivary duct carcinoma harboring HRAS G13V and PIK3CA E545K (PMID: 37427101). 37427101
HRAS Q61H uterine cancer sensitive BTX-6654 Preclinical - Cell culture Actionable In a preclinical study, BTX-6654 inhibited proliferation of a uterine cancer cell line harboring HRAS Q61H in 3D culture (PMID: 38224565). 38224565
HRAS Q61H uterine cancer sensitive BTX-7312 Preclinical - Cell culture Actionable In a preclinical study, BTX-7312 inhibited proliferation of a uterine cancer cell line harboring HRAS Q61H in 3D culture (PMID: 38224565). 38224565
HRAS Q61L lung squamous cell carcinoma no benefit Buparlisib Preclinical - Cell culture Actionable In a preclinical study, BKM120 did not inhibit growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 26544513) 26544513
HRAS Q61L Advanced Solid Tumor sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing HRAS Q61L demonstrated sensitivity to growth inhibition by Afinitor (everolimus) in culture (PMID: 26544513). 26544513
HRAS Q61L Advanced Solid Tumor sensitive Binimetinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing HRAS Q61L demonstrated sensitivity to growth inhibition by Binimetinib (MEK162) in culture (PMID: 26544513). 26544513
HRAS Q61L lung squamous cell carcinoma sensitive Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) inhibited growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture, and inhibited tumor growth in xenograft models (PMID: 26544513). 26544513
HRAS Q61L head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Cell line xenograft Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line xenograft model harboring HRAS Q61L was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth and vessel formation, increased apoptotic activity, and decreased cell proliferation (PMID: 32727882). 32727882
HRAS Q61L head and neck squamous cell carcinoma sensitive Sirolimus + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Rapamune (sirolimus) worked synergistically with Mekinist (trametinib) to inhibit proliferation of head and neck squamous carcinoma cell lines harboring HRAS Q61L in culture and to reduce tumor growth in cell line xenograft models (PMID: 26882569). 26882569
HRAS Q61L skin squamous cell carcinoma no benefit PLX7904 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX7904 did not stimulate growth of Zelboraf (vemurafenib)-induced cutaneous squamous cell carcinoma cells harboring HRAS Q61L in culture or in cell line xenograft models (PMID: 26466569). 26466569
HRAS Q61L lung squamous cell carcinoma sensitive Everolimus + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Selumetinib (AZD6244) and Afinitor (everolimus) inhibited growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture, and inhibited tumor growth in xenograft models, with increased efficacy compared to either agent alone (PMID: 26544513). 26544513
HRAS Q61L lung squamous cell carcinoma sensitive Binimetinib + Everolimus Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 26544513). 26544513
HRAS Q61L Advanced Solid Tumor sensitive Binimetinib + Everolimus Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) worked synergistically to inhibit growth of transformed cells expressing HRAS Q61L in culture (PMID: 26544513). 26544513
HRAS Q61L lung squamous cell carcinoma sensitive AZD8055 + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and AZD8055 reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 26544513). 26544513
HRAS Q61L Advanced Solid Tumor sensitive NS1 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing HRAS Q61L demonstrated sensitivity to NS1, resulting in inhibition of Mapk and Akt signaling and cell transformation in culture (PMID: 27820802). 27820802
HRAS Q61L head and neck squamous cell carcinoma sensitive SCH772984 + Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, the addition of SCH772984 sensitized head and neck squamous cell carcinoma cell lines harboring HRAS Q61L to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). 35247914
HRAS Q61L head and neck squamous cell carcinoma sensitive Tipifarnib + Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, combination treatment with Ulixertinib (BVD-523) and Zarnestra (tipifarnib) resulted in a synergistic effect, with enhanced apoptosis in a head and neck squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 35247914). 35247914
HRAS Q61L esophageal cancer sensitive IHMT-RAF-128 Preclinical - Cell culture Actionable In a preclinical study, IHMT-RAF-128 inhibited proliferation in an esophageal cancer cell line harboring HRAS Q61L in culture (PMID: 37164118). 37164118
BRAF D594E HRAS Q61L melanoma sensitive NST-628 Preclinical - Pdx Actionable In a preclinical study, NST-628 treatment resulted in an overall response rate of 69.5% in a panel of patient-derived xenograft (PDX) models of solid tumors harboring RAS-MAPK pathway alterations, including a response in a melanoma patient-derived xenograft (PDX) model harboring BRAF D594E and HRAS Q61L (PMID: 38588399). 38588399
ALK F1174L HRAS Q61L neuroblastoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, HRAS Q61L was identified in a post-progression biopsy in a pediatric patient with metastatic neuroblastoma harboring ALK F1174L, who previously achieved a partial response on Lorbrena (lorlatinib) treatment (PMID: 39177282). 39177282
HRAS Q61R Advanced Solid Tumor sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing HRAS Q61R demonstrated sensitivity to growth inhibition by Afinitor (everolimus) in culture (PMID: 26544513). 26544513
HRAS Q61R Advanced Solid Tumor sensitive Binimetinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing HRAS Q61R demonstrated sensitivity to growth inhibition by Binimetinib (MEK162) in culture (PMID: 26544513). 26544513
HRAS Q61R bladder urothelial carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, 2 patients with bladder urothelial carcinoma harbored HRAS Q61R achieved partial responses (PMID: 32636318; NCT02535650). 32636318
HRAS K117N head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Pdx Actionable In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS K117N was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). 32727882
FGFR3 K650E FGFR3 over exp HRAS K117E multiple myeloma sensitive PD173074 Preclinical - Cell culture Actionable In a preclinical study, PD173074 inhibited Fgfr3 signaling, induced cell cycle arrest, and decreased proliferation of multiple myeloma cells harboring HRAS K117E and overexpression of FGFR3 K650E in culture (PMID: 22869148). 22869148
FGFR3 K650E FGFR3 over exp HRAS K117E myeloid neoplasm sensitive AZ8010 Preclinical Actionable In a preclinical study, AZ8010 inhibited Fgfr3 signaling and decreased proliferation of myeloma cells with HRAS K117E and overexpression of FGFR3 K650E in culture (PMID: 22869148). 22869148
HRAS act mut Advanced Solid Tumor no benefit Selumetinib Clinical Study - Cohort Actionable In a Phase II trial (Pediatric MATCH), Koselugo (selumetinib) treatment was tolerated but did not result in an objective response in pediatric patients with advanced solid tumors including high-grade glioma (n=8) and rhabdomyosarcoma (n=7) harboring MAPK pathway alterations including BRAF V600E (n=2), activating KRAS (n=8)/HRAS (n=1)/NRAS (n=3) or inactivating NF1 (n=7) mutations, with a 6-month progression-free survival of 15% (3/20) and 3 stable disease as best response (PMID: 35363510; NCT03213691). 35363510
HRAS act mut transitional cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated safety and preliminary efficacy in patients with metastatic urothelial carcinoma harboring HRAS mutations (n=14) or STK11:rs2075606, 3 of 4 patients achieved progression-free survival at 6 months harbored HRAS activating mutations, and no response was observed in HRAS wild-type patients (J Clin Oncol 38: 2020 (suppl; abstr 5086); NCT02535650). detail...
HRAS act mut salivary gland carcinoma sensitive Tipifarnib Clinical Study Actionable In a clinical study, Zarnestra (tipifarnib) treatment resulted in an overall response rate of 8% (n=13) with one ongoing partial response with a duration of 14 months and stable disease as the best response in 58% (7/12) of evaluable patients with HRAS-mutant metastatic salivary gland carcinoma, and a median overall survival of 18 months, and a median progression-free survival of 7 months (PMID: 32557577). 32557577
HRAS act mut Advanced Solid Tumor predicted - sensitive BAY 11-7082 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY 11-7082 induced apoptosis and decreased Akt signaling, viability, and colony formation in cancer cells harboring activating HRAS mutations in culture and inhibited tumor growth in a cell line xenograft model (PMID: 38982514). 38982514
EML4 - ALK HRAS amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, HRAS amplification (PMID: 29636358). 29636358
HRAS A146T head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Pdx Actionable In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS A146T was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). 32727882
HRAS over exp head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Pdx Actionable In a preclinical study, Zarnestra (tipifarnib) treatment resulted in tumor regression in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma overexpressing wild-type Hras (J Clin Oncol 38: 2020 (suppl; abstr e15658)). detail...
HRAS over exp head and neck squamous cell carcinoma sensitive Alpelisib + Tipifarnib Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination of Piqray (alpelisib) and Zarnestra (tipifarnib) inhibited Mtor and Rsk phosphorylation, induced cell cycle arrest and apoptosis, and synergistically inhibited viability of an HRAS-overexpressing head and neck squamous cell carcinoma cell line in culture and inhibited tumor growth in patient-derived xenograft (PDX) models (PMID: 37339176). 37339176
HRAS over exp head and neck squamous cell carcinoma sensitive Alpelisib + Tipifarnib Preclinical - Pdx Actionable In a preclinical study, Zarnestra (tipifarnib) and Piqray (Alpelisib) combination treatment resulted in enhanced tumor regression in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma overexpressing wild-type Hras (J Clin Oncol 38: 2020 (suppl; abstr e15658)). detail...
HRAS over exp head and neck squamous cell carcinoma predicted - sensitive Tipifarnib + Uprosertib Preclinical - Pdx Actionable In a preclinical study, Zarnestra (tipifarnib) and Uprosertib (GSK2141795) combination treatment resulted in enhanced tumor regression in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma overexpressing wild-type Hras (J Clin Oncol 38: 2020 (suppl; abstr e15658)). detail...
HRAS over exp head and neck squamous cell carcinoma predicted - sensitive Sapanisertib + Tipifarnib Preclinical - Pdx Actionable In a preclinical study, Zarnestra (tipifarnib) and Sapanisertib (MLN0128) combination treatment resulted in enhanced tumor regression in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma overexpressing wild-type Hras (J Clin Oncol 38: 2020 (suppl; abstr e15658)). detail...
HRAS V29Cfs*19 bladder urothelial carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with bladder urothelial carcinoma harboring HRAS V29Cfs*19 achieved a partial response (PMID: 32636318; NCT02535650). 32636318