Gene Variant Detail

Gene KRAS
Variant G12D
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions KRAS G12D is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12D results in decreased Kras GTPase activity and increased activation of downstream signaling, promotes tumor formation in mouse models (PMID: 16474405, PMID: 26037647, PMID: 22871572) and is transforming in cell culture (PMID: 29533785).
Associated Drug Resistance

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Transcript NM_033360
gDNA chr12:g.25245350C>T
cDNA c.35G>A
Protein p.G12D
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_033360 chr12:g.25245350C>T c.35G>A p.G12D RefSeq GRCh38/hg38
XM_011520653 chr12:g.25245350C>T c.35G>A p.G12D RefSeq GRCh38/hg38
XM_006719069 chr12:g.25245350C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_004985 chr12:g.25245350C>T c.35G>A p.G12D RefSeq GRCh38/hg38
XM_017019293 chr12:g.25245350C>T c.35G>A p.G12D RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS G12D TP53 S127Y lung adenocarcinoma sensitive Dasatinib + Demcizumab Preclinical - Pdx Actionable In a preclinical study, combination of Sprycel (dasatinib) and Demcizumab (OMP-21M18) treatment resulted in durable tumor inhibition in patient-derived animal models of lung adenocarcinoma harboring KRAS G12D and TP53 S127Y (PMID: 26855149). 26855149
BRAF V600E KRAS G12D colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquisition of KRAS G12D (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer resistant LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer sensitive Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
KRAS G12D PTPN11 loss pancreatic ductal adenocarcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, CRISPR-Cas9-mediated knock-out of PTPN11 abolished reactivation of MAPK signaling in the presence of Mekinist (trametinib) in pancreatic ductal adenocarcinoma cells harboring KRAS G12D, resulted in enhanced growth inhibition in culture (PMID: 29808009). 29808009
KRAS G12D PTPN11 loss pancreatic ductal adenocarcinoma sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, CRISPR-Cas9-mediated knock-out of PTPN11 abolished reactivation of MAPK signaling in the presence of Selumetinib (AZD6244) in pancreatic ductal adenocarcinoma cells harboring KRAS G12D, resulted in enhanced growth inhibition in culture (PMID: 29808009). 29808009
KRAS G12D MET over exp stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human gastric cancer cell line with high levels of MET expression and expressing KRAS G12D was resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26432108). 26432108
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Sprycel (dasatinib) induced growth inhibition in culture and in xenograft models (PMID: 27231123). 27231123
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition in culture (PMID: 27231123). 27231123
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma sensitive SRA737 Preclinical Actionable In a preclinical study, SRA737 (CCT245737) resulted in some decreased tumor volume in a pancreatic ductal adenocarcinoma transgenic mouse model harboring KRAS G12D and TP53 R175H when compared to control (PMID: 27167172). 27167172
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma sensitive Gemcitabine + SRA737 Preclinical Actionable In a preclinical study, Gemzar (gemcitabine) resulted in enhanced antitumor efficacy, including decreased tumor volume, when combined with SRA737 (CCT245737) in a pancreatic ductal adenocarcinoma transgenic mouse model harboring KRAS G12D and TP53 R175H (PMID: 27167172). 27167172
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma conflicting Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) treatment in transgenic animal models of pancreatic ductal adenocarcinoma harboring KRAS G12D and TP53 R175H resulted in proliferation of tumor cells in interior, hypovascularized tumor regions, but inhibited proliferation in outer, vascularized tumor regions, despite inhibition of mTORC signaling in both regions (PMID: 26144316). 26144316
KRAS G12D TP53 R175H pancreatic cancer sensitive Pimasertib + Gemcitabine Preclinical Actionable In a preclinical study, the combination of pimasertib and Gemzar (gemcitabine) inhibited tumor growth in a syngeneic mouse model of pancreatic cancer expressing KRAS G12D and TP53 R175H (PMID: 26228206). 26228206
PTEN pos KRAS G12D endometrial cancer sensitive Metformin Preclinical - Cell line xenograft Actionable In a preclinical study, Glucophage (metformin) inhibited cell proliferation and induced apoptosis in a PTEN-expressing human endometrial cancer cell line harboring KRAS G12D in culture and decreased tumor growth in xenograft models (PMID: 24077915). 24077915
BRAF G464E KRAS G12D melanoma predicted - resistant Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G464E and KRAS G12D in culture (PMID: 29903896). 29903896
BRAF G464E KRAS G12D melanoma sensitive Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G464E and KRAS G12D in culture (PMID: 29903896). 29903896
KRAS G12D MET amp esophageal carcinoma resistant AMG 337 Clinical Study Actionable In a clinical case study, a patient with a MET amplified esophageal carcinoma that initially responded to AMG 337, developed resistance upon emergence of KRAS G12D (PMID: 26432108). 26432108
KRAS G12D colorectal cancer sensitive KRAS mutant-specific TIL Clinical Study Actionable In a clinical case study, a patient with metastatic colorectal cancer harboring KRAS G12D demonstrated regression of metastatic lung lesions and a partial response for 9 months following infusion of autologous tumor-infiltrating lymphocytes containing cytotoxic T-cells that specifically recognize KRAS G12D (PMID: 27959684). 27959684
KRAS G12D pancreatic cancer decreased response Pictilisib Preclinical - Cell line xenograft Actionable In a preclinical study, Pictilisib (GDC-0941) demonstrated limited efficacy as a single agent in a pancreatic cell line xenograft model harboring KRAS G12D (PMID: 22952903). 22952903
KRAS G12D lung adenocarcinoma decreased response Selumetinib Preclinical Actionable In a preclinical study, the treatment of a mouse model lung adenocarcinoma harboring the KRAS G12D mutant with selumetinib, a MEK inhibitor, resulted in modest tumor regression (PMID: 19029981). 19029981
KRAS G12D lung adenocarcinoma sensitive Selumetinib + BEZ235 Preclinical Actionable In a preclinical study, a mouse lung adenocarcinoma model harboring the KRAS G12D mutation treated with a combination of the MEK inhibitor selumetinib (AZD6244) and the PI3K inhibitor BEZ235 resulted in significant tumor regression (PMID: 19029981). 19029981
KRAS G12D pancreatic ductal adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells harboring KRAS G12D demonstrated reduced sensitivity to Selumetinib (AZD6244) in culture when compared to the combined therapy of Selumetinib (AZD6244) and SHP099 (PMID: 30045908). 30045908
KRAS G12D pancreatic cancer resistant UC-773587 Preclinical Actionable In a preclinical study, UC-773587 did not inhibit growth of pancreatic cancer cells harboring KRAS G12D in culture (PMID: 25825487). 25825487
KRAS G12D colon cancer sensitive Luminespib Preclinical - Cell culture Actionable In a preclinical study, Luminespib (AUY922) inhibited growth of a colon cancer cell line harboring KRAS G12D in culture (PMID: 26832792). 26832792
KRAS G12D colorectal cancer resistant Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) treatment resulted in continued tumor growth in xenograft models of patient derived colorectal cancer cells harboring KRAS G12D (PMID: 26243863). 26243863
KRAS G12D Advanced Solid Tumor sensitive AZD8055 + MK-1775 Preclinical Actionable In a preclinical study, AZD8055 worked synergistically with MK-1775 to inhibit proliferation and promote apoptosis in transformed cells expressing KRAS G12D in culture (PMID: 24791855). 24791855
KRAS G12D lung cancer predicted - sensitive AR-mTOR-26 Preclinical - Cell line xenograft Actionable In a preclinical study, AR-mTOR-26 treatment resulted in antitumor activity in lung cancer cell line xenograft models harboring KRAS G12D (Cancer Res 2010;70(8 Suppl):Abstract nr 4484). detail...
KRAS G12D lung cancer predicted - resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 did not inhibit growth of lung cancer cells harboring KRAS G12D in 3D culture (PMID: 30104724). 30104724
KRAS G12D pancreatic cancer resistant UC-857993 Preclinical Actionable In a preclinical study, UC-857993 did not inhibit growth of pancreatic cancer cells harboring KRAS G12D in culture (PMID: 25825487). 25825487
KRAS G12D lung adenocarcinoma sensitive PX-866 Preclinical Actionable In a preclinical study, the treatment of KRAS G12D mutant mouse lung cancer with PX-866, a PI3K inhibitor, resulted in inhibition of tumor growth (PMID: 18493606). 18493606
KRAS G12D pancreatic cancer sensitive AZD4785 Preclinical - Cell culture Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of pancreatic cancer cells harboring KRAS G12D (PMID: 28615361). 28615361
KRAS G12D lung adenocarcinoma sensitive PD-0325901 Preclinical Actionable In a preclinical study, PD-0325901 inhibited growth of lung adenocarcinomas in mouse models expressing Kras G12D (PMID: 22684718). 22684718
KRAS G12D colorectal cancer resistant Sunitinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring the KRAS G12D mutation showed resistance to Sutent (sunitinib) treatment (PMID: 23455880). 23455880
KRAS G12D pancreatic cancer predicted - sensitive Aphanin Preclinical - Cell culture Actionable In a preclinical study, Aphanin inhibited proliferation and induced apoptosis in pancreatic cancer cells harboring KRAS G12D in culture (PMID: 27333990). 27333990
KRAS G12D lung cancer no benefit BEZ235 Preclinical Actionable In a preclinical study, BEZ235 did not induce tumor shrinkage in mouse lung cancer models carrying KRAS G12D (PMID: 19029981). 19029981
KRAS G12D myelodysplastic/myeloproliferative neoplasm sensitive Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) demonstrated efficacy in a mouse model of chronic myelomonocytic leukemia expressing KRAS G12D (ASH Annual Meeting Abstracts 2012 120: 2862). detail...
KRAS G12D ovary epithelial cancer predicted - sensitive MEK162 + Paclitaxel Clinical Study Actionable In a Phase Ib trial, Taxol (paclitaxel) and Mektovi (binimetinib) combination therapy demonstrated clinical benefit in three patients with platinum resistant/refractory epithelial ovarian cancer harboring activating mutations in KRAS, with one partial response and one stable disease in patients with KRAS G12D and stable disease in a patient with KRAS G12V (PMID: 29844129; NCT01649336). 29844129
KRAS G12D pancreatic ductal adenocarcinoma sensitive GS-493 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, GS-493 and Selumetinib (AZD6244) synergistically inhibited growth of pancreatic ductal adenocarcinoma cells harboring KRAS G12D in culture (PMID: 29808009). 29808009
KRAS G12D colon cancer predicted - resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 did not inhibit growth of colon cancer cells harboring KRAS G12D in 3D culture (PMID: 30104724). 30104724
KRAS G12D lung cancer sensitive SH-1242 Preclinical Actionable In a preclinical study, SH-1242 inhibited lung tumor growth in a KRAS G12D-expressing transgenic mouse model that forms spontaneous lung tumors (PMID: 26645561). 26645561
KRAS G12D pancreatic ductal adenocarcinoma sensitive SHP099 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, SHP099 and Mekinist (trametinib) synergistically inhibited growth of pancreatic ductal adenocarcinoma cells harboring KRAS G12D in culture, and inhibited tumor growth in patient-derived xenograft (PDX) models (PMID: 29808009). 29808009
KRAS G12D colorectal cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited growth of colorectal cancer cells harboring KRAS G12D in 3D culture (PMID: 30104724). 30104724
KRAS G12D stomach cancer sensitive BKM120 + AG490 Preclinical Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Tyrphostin B42 (AG-490) worked synergistically to inhibit proliferation and induce apoptosis in gastric cancer cell lines harboring KRAS G12D in culture (PMID: 22159814). 22159814
KRAS G12D colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 resulted in tumor regression in a patient-derived xenograft model of colorectal cancer harboring KRAS G12D, but relapse upon discontinuation of treatment (PMID: 28611205). 28611205
KRAS G12D pancreatic cancer sensitive rigosertib Preclinical Actionable In a preclinical study, Estybon (rigosertib) inhibited tumorigenesis in transgenic animal model of pancreatic cancer driven by KRAS G12D (PMID: 27104980). 27104980
KRAS G12D colorectal cancer resistant Neratinib + Trastuzumab Preclinical Actionable In a preclinical study, Herceptin (trastuzumab) and Nerlynx (neratinib) combination treatment resulted in continued tumor growth in xenograft models of patient derived colorectal cancer cells harboring KRAS G12D (PMID: 26243863). 26243863
KRAS G12D colorectal cancer sensitive Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in patient-derived xenograft models of colorectal cancer harboring KRAS G12D (PMID: 28611205). 28611205
KRAS G12D lung cancer sensitive Selumetinib + BEZ235 Preclinical Actionable In a preclinical study, BEZ235 in combination with Selumetinib (AZD6244) induced tumor shrinkage in mouse lung cancer models carrying KRAS G12D (PMID: 19029981). 19029981
KRAS G12D biliary tract cancer sensitive Copanlisib + Refametinib Preclinical Actionable In a preclinical study, Aliqopa (copanlisib) and Refametinib (BAY86-9766) worked synergistically to inhibit proliferation and increase apoptosis of biliary tract cancer cells harboring KRAS G12D in culture (Cancer Res April 15, 2012 72:869). detail...
KRAS G12D pancreatic cancer predicted - resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 did not inhibit growth of pancreatic cancer cells harboring KRAS G12D in 3D culture (PMID: 30104724). 30104724
KRAS G12D Advanced Solid Tumor sensitive LY294002 Preclinical Actionable In a preclinical study, LY294002 reduced phosphorylation of Akt in pancreatic epithelial cells expressing Kras G12D (PMID: 22871572). 22871572
KRAS G12D colorectal cancer sensitive PD-0325901 + ZSTK474 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination treatment of PD-0325901 and ZSTK474 inhibited tumor growth of colorectal cancer cell line xenograft models harboring KRAS G12D (PMID: 28775144). 28775144
KRAS G12D pancreatic cancer sensitive Pictilisib + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Pictilisib (GDC-0941) and Selumetinib (AZD6244) worked synergistically to induce tumor regression in a pancreatic cancer cell line xenograft model harboring KRAS G12D (PMID: 22952903). 22952903
KRAS G12D colorectal cancer sensitive ST-162 Preclinical - Cell line xenograft Actionable In a preclinical study, ST-162 treatment inhibited tumor growth of colorectal cancer cell line xenograft models harboring KRAS G12D (PMID: 28775144). 28775144
KRAS G12D pancreatic ductal adenocarcinoma sensitive GS-493 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, GS-493 and Mekinist (trametinib) synergistically inhibited growth of pancreatic ductal adenocarcinoma cells harboring KRAS G12D in culture (PMID: 29808009). 29808009
KRAS G12D pancreatic adenocarcinoma sensitive RAF709 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, RAF709 and Mekinist (trametinib) synergistically inhibited Erk signaling and growth of pancreatic adenocarcinoma cells in culture, resulted in tumor regression in cell line xenograft models (PMID: 29343524). 29343524
KRAS G12D pancreatic ductal adenocarcinoma sensitive Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Selumetinib (AZD6244) and SHP099 resulted in a synergistic effect, demonstrating reduced cell proliferation and decreased colony formation in pancreatic ductal adenocarcinoma cells harboring KRAS G12D (PMID: 30045908). 30045908
KRAS G12D pancreatic cancer sensitive Ponatinib + Trametinib Preclinical Actionable In a preclinical study, the combination of Mekinist (trametinib) and Iclusig (ponatinib) induced cell death in tumors and prolonged survival in an animal model of pancreatic cancer harboring KRAS G12D (PMID: 27338794). 27338794
KRAS G12D cholangiocarcinoma sensitive TAK-733 Preclinical - Pdx Actionable In a preclinical study, TAK-733 induce tumor regression in patient derived xenografts of cholangiocarcinoma with Kras G12D mutations (AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2523). detail...
KRAS G12D pancreatic cancer sensitive Reolysin + Gemcitabine Clinical Study Actionable In a clinical case report, treatment with Reolysin (pelareorep) in combination with Gemzar (gemcitabine) resulted in stable disease in a patient with pancreatic cancer harboring KRAS G12D (PMID: 26156229). 26156229
KRAS G12D PTEN loss TP53 V216M colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12D, PTEN loss, and TP53 V216M (PMID: 26272063). 26272063
PTEN loss KRAS G12D pancreatic adenocarcinoma sensitive MK2206 Phase I Actionable In a Phase I study, a patient with pancreatic adenocarcinoma harboring PTEN loss and KRAS G12D was treated with MK-2206 and demonstrated a 23% reduction in tumor size (PMID: 22025163). 22025163
APC inact mut KRAS G12D PTEN inact mut colorectal cancer sensitive BEZ235 + Binimetinib Preclinical Actionable In a preclinical study, combination of BEZ235 and Binimetinib (MEK162) increased survival compared to single agent in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation and KRAS G12D (PMID: 26206338). 26206338
APC inact mut KRAS G12D PTEN inact mut colorectal cancer sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 inhibited mTOR signaling in tumors and increased survival in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation, and KRAS G12D (PMID: 26206338). 26206338
APC inact mut KRAS G12D PTEN inact mut colorectal cancer no benefit Binimetinib Preclinical Actionable In a preclinical study, Binimetinib (MEK162) increased both apoptosis and proliferation in tumors, resulted in no improvement in survival in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation and KRAS G12D (PMID: 26206338). 26206338
KRAS G12D STK11 loss non-small cell lung carcinoma predicted - sensitive MK-1775 + Cisplatin Preclinical Actionable In a preclinical study, MK-1775 and Platinol (cisplatin) combination treatment resulted in improved survival in transgenic animal models of non-small cell lung carcinoma harboring KRAS G12D and STK11 loss compared to Platinol (cisplatin) alone (PMID: 28652249). 28652249
APC inact mut KRAS G12D colorectal cancer sensitive Binimetinib Preclinical Actionable In a preclinical study, Binimetinib (MEK162) increased apoptosis in tumors and improved survival in transgenic animal models of colorectal cancer driven by APC inactivation and KRAS G12D (PMID: 26206338). 26206338
APC inact mut KRAS G12D colorectal cancer sensitive BEZ235 + Binimetinib Preclinical Actionable In a preclinical study, combination of BEZ235 and Binimetinib (MEK162) resulted in reduced tumor growth and additive effect on survival compared to single agent in transgenic animal models of colorectal cancer driven by APC inactivation and KRAS G12D (PMID: 26206338). 26206338
APC inact mut KRAS G12D colorectal cancer sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 inhibited PI3K/mTOR signaling in tumors and increased survival in transgenic animal models of colorectal cancer driven by APC inactivation and KRAS G12D (PMID: 26206338). 26206338
KRAS G12D EZH2 pos lung adenocarcinoma sensitive DZNep + MK2206 Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of DZNep increased sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12D in culture and in xenograft models, resulting in decreased cell survival and tumor growth (PMID: 26676756). 26676756
KRAS G12D EZH2 pos lung adenocarcinoma no benefit Selumetinib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, the addition of Tazemetostat (EPZ-6438) did not increase sensitivity to Selumetinib (AZD6244) in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12D (PMID: 26676756). 26676756
KRAS G12D EZH2 pos colon cancer no benefit DZNep + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep did not increase sensitivity to Selumetinib (AZD6244) in an EZH2-expressing colon cancer cell line harboring KRAS G12D in culture (PMID: 26676756). 26676756
KRAS G12D EZH2 pos colon cancer sensitive DZNep + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep increased sensitivity to MK2206 in an EZH2-expressing colon cancer cell line harboring KRAS G12D in culture (PMID: 26676756). 26676756
KRAS G12D EZH2 pos lung adenocarcinoma no benefit DZNep + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep did not increase sensitivity to Selumetinib (AZD6244) in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12D (PMID: 26676756). 26676756
KRAS G12D EZH2 pos lung adenocarcinoma no benefit GSK343 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of GSK343 did not increase sensitivity to Selumetinib (AZD6244) in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12D (PMID: 26676756). 26676756
KRAS G12D EZH2 pos lung adenocarcinoma sensitive GSK343 + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of GSK343 increased sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12D in culture (PMID: 26676756). 26676756
KRAS G12D EZH2 pos pancreatic cancer no benefit DZNep + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep did not increase sensitivity to Selumetinib (AZD6244) in an EZH2-expressing pancreatic cancer cell line harboring KRAS G12D in culture (PMID: 26676756). 26676756
KRAS G12D EZH2 pos lung adenocarcinoma sensitive MK2206 + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, the addition of Tazemetostat (EPZ-6438) increased sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12D in culture (PMID: 26676756). 26676756
KRAS G12D EZH2 pos pancreatic cancer sensitive DZNep + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep increased sensitivity to MK2206 in an EZH2-expressing pancreatic cancer cell line harboring KRAS G12D in culture (PMID: 26676756). 26676756
KRAS G12D STK11 inact mut lung cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, Sapanisertib (MLN0128) inhibited lung tumor growth in mouse models with KRAS G12D and inactivation of STK11 (LKB1), and demonstrated limited efficacy in tumors with KRAS G12D and wild-type STK11 (PMID: 26574479). 26574479
KRAS G12D PTEN dec exp TP53 R306* colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12D, decreased PTEN expression, and TP53 R306* (PMID: 26272063). 26272063
ATM del KRAS G12D lung adenocarcinoma sensitive VX-970 Preclinical Actionable In a preclinical study, a KRAS G12D driven lung adenocarcinoma mouse model with homozygous deletion of ATM was sensitive to VX-970, demonstrating decreased tumor volume and greater overall survival compared to control treated models (PMID: 28363999). 28363999
ATM del KRAS G12D lung adenocarcinoma sensitive Olaparib Preclinical Actionable In a preclinical study, a KRAS G12D driven lung adenocarcinoma mouse model with homozygous deletion of ATM was sensitive to Lynparza (olaparib), demonstrating reduced tumor volume and greater overall survival when compared to models treated with control (PMID: 28363999). 28363999
BRAF wild-type KRAS G12D pancreatic cancer resistant GDC0879 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type pancreatic cancer cells harboring KRAS G12D in cell line xenograft models (PMID: 19276360). 19276360
KRAS G12D PTPN11 E76A pancreatic ductal adenocarcinoma resistant Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) in combination with SHP099 did not inhibit growth of pancreatic ductal adenocarcinoma harboring KRAS G12D and expressing PTPN11 E76A in culture (PMID: 29808009). 29808009
KRAS G12D PTPN11 E76A pancreatic ductal adenocarcinoma sensitive GS-493 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) in combination with GS-493 inhibited growth of pancreatic ductal adenocarcinoma harboring KRAS G12D and expressing PTPN11 E76A in culture (PMID: 29808009). 29808009