Molecular Profile Detail

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 pancreatic cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) 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 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 pancreatic adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 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 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 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 pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 lung adenocarcinoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 pancreatic cancer sensitive AZD4785 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 cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) 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 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 biliary tract cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PIK3CA inhibitor 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 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 Advanced Solid Tumor sensitive PI3K Inhibitor (Pan) 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 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 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 pancreatic cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) 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 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 adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) 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 MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 stomach cancer sensitive PI3K Inhibitor (Pan) 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 myelodysplastic/myeloproliferative neoplasm sensitive PI3K Inhibitor (Pan) 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 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 pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 cholangiocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 decreased response PI3K Inhibitor (Pan) 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 Advanced Solid Tumor sensitive PI3K Inhibitor (Pan) LY294002 Preclinical Actionable In a preclinical study, LY294002 reduced phosphorylation of Akt in pancreatic epithelial cells expressing Kras G12D (PMID: 22871572). 22871572
KRAS G12D lung adenocarcinoma sensitive PI3K Inhibitor (Pan) 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 ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 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 lung cancer no benefit PI3K Inhibitor (Pan) 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 pancreatic cancer sensitive PI3K Inhibitor (Pan) 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 pancreatic cancer sensitive RAS Inhibitor (Pan) 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
Clinical Trial Phase Therapies Title Recruitment Status
NCT01833143 Phase II Bortezomib Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D Active, not recruiting
NCT03745326 Phase Ib/II Aldesleukin + anti-KRAS G12D mTCR cells + Cyclophosphamide + Fludarabine Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients Recruiting