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BIOMARKER:

KRAS A146

i
Other names: KRAS, KRAS1, KRAS2, Kirsten rat sarcoma viral oncogene homolog
Entrez ID:
Related biomarkers:
1m
A Facile Method to Append a Bio-ID Tag to Endogenous Mutant Kras Alleles. (PubMed, Methods Mol Biol)
These proteins are captured through the strong interaction between the biotin label and streptavidin bead and subsequently identified by mass spectrometry. Here, we developed a protocol using CRISPR-mediated gene editing to generate endogenous BioID2-tagged KrasG12D and KrasG12V isogenic murine colon epithelial cell lines to identify unique protein proximity partners by BioID.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12 • KRAS A146 • KRAS Q61
7ms
Genome Sequencing to Discover Drivers of Clonal Expansion in Smoldering Multiple Myeloma (ASH 2023)
In addition to well-characterized MM drivers (KRAS, NRAS, etc.), 16 new candidate genes were found significantly mutated, including IKFZ3 (Aiolos), a transcription factor and direct target of degradation with lenalidomide therapy, harboring frameshift and stop-gain mutations in the protein dimerization domain which could affect complete differentiation of plasma cells...Conclusion These results highlight the power of genomic profiling in MM for early detection, discovery of novel drivers, monitoring of clonal selection and transformation to malignant disease. We show SMM is not a simple genomically-mature disorder, but rather a dynamic state with competing subclones, which could be leveraged for therapeutic interventions.
IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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KRAS mutation • KRAS G12 • NRAS Q61 • KRAS G12S • KRAS G13 • NRAS G13 • KRAS A146 • KRAS Q61 • NRAS A146 • Chr del(1p) • NRAS G12S
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lenalidomide
7ms
Secondary Genetic Events Impact the Expression of Key Immunotargets on the Surface of Multiple Myeloma Cells (ASH 2023)
dSTORM imaging of cell line models carrying patient-derived secondary genetic alterations revealed a distinct pattern linked to each mutation respectively. In KRASG12A, we observed a reduction in BCMA density by 2-fold as compared to wild type cells (5.9 ± 0.3 vs. 10.8 ± 1.2 localization clusters/µm2, p=0005).
IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • SDC1 (Syndecan 1) • SLAMF7 (SLAM Family Member 7)
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TP53 mutation • KRAS mutation • TP53 deletion • KRAS G12A • KRAS G12 • KRAS A146 • KRAS A146T
11ms
Characterization of the immune and genomic profile of a large cohort of advanced KRAS-driven non-small cell lung cancer (EACR 2023)
KRAS is a complex genetic mutation associated with heterogeneity in PD-L1 expression and co-alterations, which could serve as biomarkers for differential outcomes. STK11 co-mutation appears to be a poor prognostic biomarker in this context.
PD(L)-1 Biomarker • IO biomarker • Metastases
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)
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PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12V • STK11 mutation • PD-L1 negative • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61
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PD-L1 IHC 22C3 pharmDx • Guardant360® CDx • InVisionFirst®-Lung
1year
SMARCB1/INI1-Deficient Poorly Differentiated Carcinoma of the Colon With Rhabdoid Features-A Rare Tumor With Serrated Phenotype: Case Report and Review of Literature. (PubMed, Int J Surg Pathol)
INI1-deficient poorly differentiated carcinoma of the colon is a rare, aggressive colonic malignancy showing a serrated phenotype. Routine identification and subtyping are important keeping in mind the distinct tumor phenotype, resistance to conventional chemotherapy, and dismal prognosis.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
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BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • RAS wild-type • NRAS wild-type • KRAS A146 • SMARCB1 mutation • NRAS A146
over1year
Preclinical • Trial termination • Combination therapy • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
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LNP3794 • BI 1701963
over1year
Driver and targetable alterations in Chinese patients with small bowel carcinoma. (PubMed, J Cancer Res Clin Oncol)
Taken together, our work provided a comprehensive analysis of driver and targetable alterations in SBA, which can facilitate the practice of precision oncology in this challenging disease.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ZKSCAN1 (Zinc Finger With KRAB And SCAN Domains 1)
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KRAS mutation • KRAS G12C • BRAF mutation • HER-2 amplification • PIK3CA mutation • KRAS wild-type • RAS mutation • RAS wild-type • KRAS G12 • KRAS A146 • KRAS Q61 • KRAS A146V • KRAS K117 • MET fusion • PIK3CA N345K • PIK3CA Q546
over1year
Trial completion
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
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LNP3794 • BI 1701963
2years
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS A146
2years
A Study to Test Different Doses of BI 1701963 in Combination With Irinotecan in People With Advanced Bowel Cancer With Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutation (clinicaltrials.gov)
P1, N=15, Terminated, Boehringer Ingelheim | N=95 --> 15 | Trial completion date: Feb 2024 --> Apr 2022 | Suspended --> Terminated | Trial primary completion date: Jan 2024 --> Apr 2022; Sponsor decision
Preclinical • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
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irinotecan • BI 1701963
2years
A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS]) (clinicaltrials.gov)
P1, N=8, Terminated, Boehringer Ingelheim | N=124 --> 8 | Trial completion date: Jul 2024 --> Apr 2022 | Suspended --> Terminated | Trial primary completion date: Oct 2023 --> Apr 2022; Sponsor decision
Preclinical • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
|
LNP3794 • BI 1701963
2years
Preclinical • Trial suspension • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
|
irinotecan • BI 1701963
2years
Preclinical • Trial suspension • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
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LNP3794 • BI 1701963
2years
Clinical impact ofKRASG12, G13, Q61, K117 and A146 mutations in patients with colorectal liver metastases (AACR 2022)
For the subgroup of patients who carried a KRAS mutation and were treated with bevacizumab and doublet or triplet chemotherapy (N=156), clinical outcome was evaluated and pretreatment tumor burden was quantified as liquid biopsy circulating tumor DNA (ctDNA) mutant allele fraction (MAF) and as total tumor volume (TTV) on CT imaging... Of the 156 patients with a KRAS mutated tumor, most carried a KRAS G12 mutation (N=112, 71.8%), followed by mutations in G13 (N=15, 9.6%), A146 (N=12, 7.7%), Q61 (N=9, 5.8%) and K117 (N=5, 3.2%). High plasma ctDNA levels were observed for patients carrying a KRAS A146 mutation versus those with a KRAS G12 mutation, with a median MAF of 48% versus 19%, respectively. Radiological TTV revealed this difference to be associated with a higher tumor load in patients harboring a KRAS A146 mutation (median TTV 672 cm3 (A146) versus 74 cm3 (G12), p=0.036).
Clinical
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS K117
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Avastin (bevacizumab)
over2years
A Study to Test Different Doses of BI 1701963 in Combination With Irinotecan in People With Advanced Bowel Cancer With Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutation (clinicaltrials.gov)
P1, N=95, Recruiting, Boehringer Ingelheim | Trial completion date: Dec 2022 --> Feb 2024 | Trial primary completion date: Oct 2022 --> Jan 2024
Preclinical • Trial completion date • Trial primary completion date • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
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irinotecan • BI 1701963
over2years
KRAS A146 Mutations Are Associated With Distinct Clinical Behavior in Patients With Colorectal Liver Metastases. (PubMed, JCO Precis Oncol)
Patients with mCRC with a KRAS A146 mutation represent a distinct molecular subgroup of patients with higher tumor burden and worse clinical outcomes, who might benefit from more intensive treatments. These results highlight the importance of testing colorectal cancer for all KRAS mutations in routine clinical care.
Clinical • Journal
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KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS K117
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Avastin (bevacizumab)
almost3years
Clinical • Preclinical • Trial completion date • Trial primary completion date • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
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LNP3794 • BI 1701963
almost3years
A Facile Method to Engineer Mutant Kras Alleles in an Isogenic Cell Background. (PubMed, Methods Mol Biol)
Therefore, selection for GFP-positive cells allows us to identify those with phenotypically silent Kras edits. Ultimately, this method allows us to toggle between different mutant alleles and preserve the wild-type allele while maintaining an isogenic background.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS expression
3years
Clinical • Enrollment open • Preclinical • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
|
LNP3794 • BI 1701963
3years
Clinical • New P1 trial • Preclinical • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
|
LNP3794 • BI 1701963
over3years
Clinical • Enrollment open • Preclinical • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
|
irinotecan • BI 1701963
over3years
Clinical • New P1 trial • Preclinical • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
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irinotecan • BI 1701963
4years
[VIRTUAL] Clonal and subclonal mutational landscapes in circulating tumor DNA in metastatic colorectal cancer: An exploratory analysis from the phase III PARADIGM study (AACR-II 2020)
The clonal and subclonal mutational landscapes of RAS WT pts were analyzed using a mCRC-focused custom ctDNA sequencing panel. Randomized pts (1:1) received mFOLFOX6 plus either panitumumab or bevacizumab. The validated ultra-deep plasma sequencing panel was concordant with tissue sequencing and detected tumor heterogeneity. The PARADIGM study will report the efficacy of anti-EGFR/VEGF therapies; post-treatment collection of ctDNA is ongoing. The relationship between therapeutic effects and clonal and subclonal mutational landscapes will be examined in the future.
P3 data
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • DNMT3A (DNA methyltransferase 1) • VEGFA (Vascular endothelial growth factor A) • TET2 (Tet Methylcytosine Dioxygenase 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • PTEN mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS A146 • KRAS Q61 • KRAS K117 • NRAS A146 • NRAS A59 • PIK3CA mutation + PTEN mutation + KRAS mutation
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Avastin (bevacizumab) • Vectibix (panitumumab)