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BIOMARKER:

KRAS Y96D

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Entrez ID:

Related biomarkers:

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STK11 deletion + KRAS mutation (6)

KRAS G12C + PD-L1 overexpression (4)

KRAS mutation + PD-L1 expression (4)

CPS1 overexpression + KRAS mutation + STK11 mutation (3)

HER-2 amplification + KRAS G12D (3)

KEAP1 deletion + KRAS mutation (3)

PD-L1 overexpression + KRAS mutation (3)

EGFR exon 19 deletion + KRAS mutation (2)

KRAS G12C + PD-L1 underexpression (2)

KRAS mutation + PD-L1 negative (2)

MSI-L/dMMR + KRAS G12V (2)

AXL overexpression + KRAS G12C (1)

CDH2 overexpression + KRAS wild-type (1)

Chr t(11;14) + KRAS mutation (1)

EGFR C797S + KRAS amplification + RB1 deletion (1)

EGFR L858R + KRAS amplification + RB1 deletion (1)

EGFR T790M + KRAS amplification + RB1 deletion (1)

EGFR V843I + KRAS G13D + AKT1 E17K + PD-L1 overexpression (1)

EGFR exon 19 deletion + TP53 mutation + CDK6 amplification + KRAS amplification (1)

EGFR expression + KRAS G12C (1)

EGFR overexpression + KRAS 13D (1)

EGFR overexpression + KRAS mutation (1)

FGFR1 overexpression + KRAS G12C (1)

GNA13 deletion + KRAS mutation (1)

GOPC-ROS1 fusion + KRAS Q61H (1)

HER-2 amplification + KRAS exon 2 wild-type (1)

HER-2 amplification + KRAS wild-type (1)

HER-2 overexpression + KRAS wild-type (1)

IGF1R overexpression + KRAS mutation (1)

IR overexpression + KRAS mutation (1)

IRS2 amplification + KRAS mutation (1)

KEAP1 mutation + KRAS wild-type (1)

KRAS A146 + TMB-H (1)

KRAS G12C + PD-L1 expression (1)

KRAS G12C + PD-L1 underexpression + STK11 mutation (1)

KRAS G12D + Chr del(9)(p21) (1)

KRAS G12D + HER-2 amplification + TMB-H (1)

KRAS G12D + TP53 deletion (1)

KRAS amplification + BRAF wild-type (1)

KRAS amplification + RAS wild-type (1)

KRAS mutation + PTPN11 overexpression + PD-L1 overexpression (1)

KRAS mutation + BCL2A1 overexpression (1)

KRAS mutation + CDK9 overexpression + HR positive (1)

KRAS mutation + EGFR amplification (1)

KRAS mutation + ER expression (1)

KRAS mutation + HER-2 positive (1)

KRAS mutation + HR positive (1)

KRAS mutation + PD-L1 underexpression (1)

KRAS mutation + PIK3CA wild-type (1)

KRAS mutation + PTPN11 overexpression (1)

KRAS mutation + TP53 mutation + GNA13 deletion (1)

KRAS mutation + TP53 mutation + PD-L1 expression + PD-1 expression (1)

KRAS mutation + YKL-40 overexpression (1)

KRAS wild-type + BRAF V600E (1)

KRAS wild-type + NRAS wild-type + MSI-H/dMMR (1)

KRAS mutation + STK11 mutation + AXL expression (1)

MLL-AFF1 fusion + KRAS mutation (1)

MSI-H/dMMR + KRAS G12D (1)

MSI-H/dMMR + KRAS Mutation (1)

MSI-H/dMMR + KRAS wild-type + BRAF wild-type (1)

MTAP deletion + KRAS G12C (1)

PD-L1 negative + KRAS G12C (1)

PD-L1 overexpression + KRAS G12C + TP53 mutation (1)

POMK-NRG1 fusion + KRAS mutation (1)

POMK‐NRG1 fusion + KRAS G12D (1)

PTEN deletion + KRAS G12C (1)

RET positive + KRAS G12V (1)

ROS1 fusion + KRAS G12C (1)

STK11 mutation + KRAS mutation + TP53 deletion (1)

STRN-ALK fusion + KRAS G13D (1)

TP53 S12F + KRAS G12D + TMB-L (1)

HER-2 amplification + KRAS G12C (0)

PRMT5 overexpression + KRAS mutation (0)

STK11 deletion + KRAS mutation (6)

KRAS G12C + PD-L1 overexpression (4)

KRAS mutation + PD-L1 expression (4)

CPS1 overexpression + KRAS mutation + STK11 mutation (3)

HER-2 amplification + KRAS G12D (3)

KEAP1 deletion + KRAS mutation (3)

PD-L1 overexpression + KRAS mutation (3)

EGFR exon 19 deletion + KRAS mutation (2)

KRAS G12C + PD-L1 underexpression (2)

KRAS mutation + PD-L1 negative (2)

MSI-L/dMMR + KRAS G12V (2)

AXL overexpression + KRAS G12C (1)

CDH2 overexpression + KRAS wild-type (1)

Chr t(11;14) + KRAS mutation (1)

EGFR C797S + KRAS amplification + RB1 deletion (1)

EGFR L858R + KRAS amplification + RB1 deletion (1)

EGFR T790M + KRAS amplification + RB1 deletion (1)

EGFR V843I + KRAS G13D + AKT1 E17K + PD-L1 overexpression (1)

EGFR exon 19 deletion + TP53 mutation + CDK6 amplification + KRAS amplification (1)

EGFR expression + KRAS G12C (1)

EGFR overexpression + KRAS 13D (1)

EGFR overexpression + KRAS mutation (1)

FGFR1 overexpression + KRAS G12C (1)

GNA13 deletion + KRAS mutation (1)

GOPC-ROS1 fusion + KRAS Q61H (1)

HER-2 amplification + KRAS exon 2 wild-type (1)

HER-2 amplification + KRAS wild-type (1)

HER-2 overexpression + KRAS wild-type (1)

IGF1R overexpression + KRAS mutation (1)

IR overexpression + KRAS mutation (1)

IRS2 amplification + KRAS mutation (1)

KEAP1 mutation + KRAS wild-type (1)

KRAS A146 + TMB-H (1)

KRAS G12C + PD-L1 expression (1)

KRAS G12C + PD-L1 underexpression + STK11 mutation (1)

KRAS G12D + Chr del(9)(p21) (1)

KRAS G12D + HER-2 amplification + TMB-H (1)

KRAS G12D + TP53 deletion (1)

KRAS amplification + BRAF wild-type (1)

KRAS amplification + RAS wild-type (1)

KRAS mutation + PTPN11 overexpression + PD-L1 overexpression (1)

KRAS mutation + BCL2A1 overexpression (1)

KRAS mutation + CDK9 overexpression + HR positive (1)

KRAS mutation + EGFR amplification (1)

KRAS mutation + ER expression (1)

KRAS mutation + HER-2 positive (1)

KRAS mutation + HR positive (1)

KRAS mutation + PD-L1 underexpression (1)

KRAS mutation + PIK3CA wild-type (1)

KRAS mutation + PTPN11 overexpression (1)

KRAS mutation + TP53 mutation + GNA13 deletion (1)

KRAS mutation + TP53 mutation + PD-L1 expression + PD-1 expression (1)

KRAS mutation + YKL-40 overexpression (1)

KRAS wild-type + BRAF V600E (1)

KRAS wild-type + NRAS wild-type + MSI-H/dMMR (1)

KRAS mutation + STK11 mutation + AXL expression (1)

MLL-AFF1 fusion + KRAS mutation (1)

MSI-H/dMMR + KRAS G12D (1)

MSI-H/dMMR + KRAS Mutation (1)

MSI-H/dMMR + KRAS wild-type + BRAF wild-type (1)

MTAP deletion + KRAS G12C (1)

PD-L1 negative + KRAS G12C (1)

PD-L1 overexpression + KRAS G12C + TP53 mutation (1)

POMK-NRG1 fusion + KRAS mutation (1)

POMK‐NRG1 fusion + KRAS G12D (1)

PTEN deletion + KRAS G12C (1)

RET positive + KRAS G12V (1)

ROS1 fusion + KRAS G12C (1)

STK11 mutation + KRAS mutation + TP53 deletion (1)

STRN-ALK fusion + KRAS G13D (1)

TP53 S12F + KRAS G12D + TMB-L (1)

HER-2 amplification + KRAS G12C (0)

PRMT5 overexpression + KRAS mutation (0)

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over1year

KRAS mutant gene editing prevents tumor growth in vivo and overcomes acquired resistance to KRASG12C inhibitor. (EACR 2023)

We demonstrated a synergistic combination between ADGN-121/Abraxane in pancreatic carcinoma and between ADGN-122/Capecitabine in colon Adenocarcinoma. We showed, that ADGN-123 containing gRNAG12C can effectively reduce the proliferation and inhibit ERK phosphorylation of sotorasib/adagrasib acquired resistance cells harboring KRASG12C/R68M and KRASG12C/Y96D mutations...ConclusionOur study provides a proof-of-concept that ADGN can be applied to target driver mutations of cancers in vivo and permanently disrupt the oncogenic alleles, leading to major tumor regression. ADGN-123 constitutes an alternative strategy to overcome resistance associated to inhibitors of KRASG12C.

over 1 year ago

Preclinical

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KRAS (KRAS proto-oncogene GTPase)

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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS Y96D • KRAS R68M • KRAS V12

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capecitabine • Lumakras (sotorasib) • albumin-bound paclitaxel • Krazati (adagrasib)

almost3years

Resistance to KRAS Inhibitors in Non-Small Cell Lung Cancer. (PubMed, Front Oncol)

Specific KRAS inhibitors, such as sotorasib and adagrasib, have been designed to bind to the protein's mutant structure and block KRAS in its GDP-bound inactive state. Acquired resistance to KRAS inhibitors include novel KRAS mutations such as Y96D/C and other RAS-MAPK effector protein mutations. This review focuses on the intrinsic and acquired mechanisms of resistance to KRAS inhibitors in KRAS mutant non-small cell lung cancer and the potential clinical strategies to overcome or prevent it.

almost 3 years ago

Review • Journal

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KRAS (KRAS proto-oncogene GTPase)

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KRAS mutation • KRAS Y96D

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Lumakras (sotorasib) • Krazati (adagrasib)