News - KRAS deletion - LARVOL VERI

11ms

Immune Checkpoint Blockade Delays Cancer Development and Extends Survival in DNA Polymerase Mutator Syndromes. (PubMed, Cancer Res)

These results demonstrated the efficiency by which cells with antigenic mutations are eliminated in vivo. Finally, ICB treatment of mutator mice earlier, before observable tumors had developed delayed cancer onset, improved survival, and selected for tumors without aneuploidy, suggesting the potential of ICB in high-risk individuals for cancer prevention.

11 months ago

Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

TP53 mutation • KRAS mutation • POLE mutation • TP53 deletion • POLD1 mutation • KRAS deletion

11ms

EZH2 deletion does not impact acinar regeneration but restricts progression to pancreatic cancer in mice. (PubMed, JCI Insight)

Loss of EZH2 did reduce recruitment of inflammatory cells and, when combined with a more aggressive PDAC model, promoted widespread PDAC progression and remodeling of the tumor microenvironment. This study suggests expression of EZH2 in adult acinar cells restricts PDAC initiation and progression by affecting both the tumour microenvironment and acinar cell differentiation.

11 months ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

KRAS G12D • KRAS G12 • EZH2 overexpression • EZH2 deletion • KRAS deletion

1year

Lfng-expressing centroacinar cell is a unique cell-of-origin for p53 deficient pancreatic cancer. (PubMed, Oncogene)

Finally, high LFNG expression is associated with high grade and poor survival in human patients. Taken together, Lfng marks a centroacinar subpopulation that is uniquely susceptible to oncogenic transformation when p53 is lost, and Lfng functions as an oncogene in all three lineages of the exocrine pancreas.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NOTCH3 (Notch Receptor 3)

TP53 mutation • KRAS mutation • TP53 deletion • KRAS deletion • KRAS mutation + TP53 mutation

1year

The Agena iPlex HS Lung Panel on the MassARRAY System Is Able to Robustly Characterize the Molecular Profile of FFPE-Derived Lung Tumor Samples Previously Deemed QNS on Multiple NGS Platforms (AMP 2024)

The Agena iPlex HS Lung Panel on the MassARRAY System is highly tolerant of poor quantity and quality DNA, recovering and delivering accurate results on samples that would otherwise fail NGS-based analysis.

1 year ago

Next-generation sequencing

EGFR (Epidermal growth factor receptor) • 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)

KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • KRAS G12V • KRAS G12 • KRAS G13 • KRAS Q61 • KRAS deletion

TruSight Oncology 500 Assay

1year

Prevalence and co-mutation status of MTAP deletions (COSA 2024)

MTAP deletions are common in the MoST/CaSP population, most frequently in CNS, pancreas, lung and melanoma patients. Detection of MTAP deletion was higher with the FM1&A paltform. MTAP deletions co-existed with CDKN2A deletions in >80% of the cohort.

1 year ago

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)

CDKN2A deletion • MTAP deletion • KRAS deletion

TruSight Oncology 500 Assay

1year

Suppression of dystroglycan function accompanies pancreatic acinar-to-ductal metaplasia and favours dysplasia development. (PubMed, J Pathol)

We conclude that dystroglycan is an important mediator of the tumour-suppressing functions of the BM during precancer evolution and that reduced dystroglycan function increases cancer risk, highlighting the dynamics of cell-BM interactions as important determinants of early cancer progression.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS deletion

1year

KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition. (PubMed, Cancer Res)

Importantly, loss of wild-type Kras sensitized Kras mutant tumors to MEK1/2 inhibition though tumors eventually became resistant and then rapidly progressed. This study demonstrates the repressive role of wild-type KRAS during pancreatic tumorigenesis and highlights the critical impact of the presence of wild-type KRAS in both tumor progression and therapeutic response in pancreatic cancer.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS wild-type • RAS wild-type • KRAS deletion

1year

Inhibition of Ribosome Biogenesis in vivo Causes p53-Dependent Death and p53-Independent Dysfunction. (PubMed, bioRxiv)

Deletion of Nat10 in acinar cells blocked Kras -oncogene-driven pancreatic intraepithelial neoplasia and subsequent pancreatic ductal adenocarcinoma, regardless of Trp53 mutation status. Together, our results provide initial insights into how cells respond to defects in RiBi and translation in vivo .

1 year ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • RPL5 (Ribosomal Protein L5) • RPL11 (Ribosomal Protein L11)

TP53 mutation • KRAS deletion

1year

Tumor immunogenicity regulates host immune responses, and conventional dendritic cell type 2 uptakes the majority of tumor antigens in an orthotopic lung cancer model. (PubMed, Cancer Immunol Immunother)

The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), whereas cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating antitumor immune responses in an orthotopic murine lung cancer model.

1 year ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • CDK1 (Cyclin-dependent kinase 1) • ITGAX (Integrin Subunit Alpha X)

TP53 mutation • KRAS mutation • TP53 deletion • KRAS deletion

1year

UBASH3B-mediated MRPL12 Y60 dephosphorylation inhibits LUAD development by driving mitochondrial metabolism reprogramming. (PubMed, J Exp Clin Cancer Res)

This study establishes MRPL12 as a novel oncogene in LUAD, contributing to LUAD pathogenesis by orchestrating mitochondrial metabolism reprogramming towards oxidative phosphorylation (OXPHOS). Furthermore, it confirms Y60 as a specific phosphorylation modification site regulating MRPL12's oncogenic functions, offering insights for the development of LUAD-specific targeted drugs and clinical interventions.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS G12D • KRAS G12 • MSH3 mutation • KRAS deletion

1year

Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma. (PubMed, Cancer Res Treat)

The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

1 year ago

Journal • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • LRP1B (LDL Receptor Related Protein 1B) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDH1 (Cadherin 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • GNAS (GNAS Complex Locus) • NFKBIA (NFKB Inhibitor Alpha 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

HER-2 mutation • LRP1B mutation • RB1 mutation • BRCA2 amplification • KRAS deletion • NOTCH mutation

1year

Targeting ALDH1A1 to enhance the efficacy of KRAS-targeted therapy through ferroptosis. (PubMed, Redox Biol)

Although the advent of sotorasib and adagrasib, has lifted the "undruggable" stigma of KRAS, the resistance to KRAS inhibitors quickly becomes a major issue. Meanwhile, we established that GTF2I is dephosphorylated at S784 via ERK by KRAS inhibitors, which hinders its nuclear translocation and mediates ALDH1A1's upregulation in response to KRAS inhibitors. In summary, the results offer valuable insights into targeting ALDH1A1 to enhance the effectiveness of KRAS-targeted therapy through ferroptosis in cancer treatment.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • GPX4 (Glutathione Peroxidase 4) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • CREB1 (CAMP Responsive Element Binding Protein 1)

KRAS deletion

Lumakras (sotorasib) • Krazati (adagrasib)