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BIOMARKER:

KRAS G12S

i
Entrez ID:
Related biomarkers:
Related tests:
6d
Anionic polymer coating for enhanced delivery of Cas9 mRNA and sgRNA nanoplexes. (PubMed, Biomater Sci)
Post-transfection, the KRAS-ERK pathway was downregulated, resulting in significant increases in cell apoptosis and inhibition of cell migration. Taken together, this study reveals a new and promising formulation for CRISPR delivery as potential lung cancer treatment.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12 • KRAS G12S
2ms
Prognostic Role of Specific KRAS Mutations Detected in Aspiration and Liquid Biopsies from Patients with Pancreatic Cancer. (PubMed, Genes (Basel))
In contrast, patients with detected KRAS G12R in the tissue survived nearly twice as long as other patients in the aggregate (286 days, 95% CI: 70-602 vs. 162 days, 95% CI: 122-600, p = 0.0374) or patients with other KRAS mutations (286 days, 95% CI: 70-602 vs. 137 days, 95% CI: 107-600, p = 0.0257). Differentiation of specific KRAS mutations in EUS-FNB and ctDNA (above all, the crucial G12D and G12R) is feasible in routine management of PDAC patients and imperative for assessment of prognosis.
Journal • Liquid biopsy • Biopsy
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12R • KRAS G12 • KRAS G12S
2ms
3D cultivation of non-small-cell lung cancer cell lines using four different methods. (PubMed, J Cancer Res Clin Oncol)
The establishment of tumoroids from lung cancer cell lines is feasible with various methodologies, which is promising for future tumoroid growth from clinical lung cancer samples. However, analysis of relevant markers is a prerequisite and may need to be validated for each model and cell type.
Preclinical • Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • NKX2-1 (NK2 Homeobox 1)
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KRAS mutation • EGFR mutation • EGFR L858R • EGFR T790M • EGFR L858R + EGFR T790M • KRAS G12 • KRAS G12S • EGFR H1975
8ms
Targeting KRAS Diversity: Covalent Modulation of G12X and Beyond in Cancer Therapy. (PubMed, J Med Chem)
This breakthrough led to the development and approval of sotorasib (AMG510) and adagrasib (MRTX849), revolutionizing the treatment of KRASG12C-dependent lung cancer. Insights from successful KRASG12C targeting informed the design of molecules addressing other mutations, often in a covalent manner. These findings offer promise for innovative approaches in addressing commonly occurring KRAS mutations such as G12D, G12V, G12A, G12S, and G12R in various cancers.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • RAS mutation • KRAS G12A • KRAS G12 • KRAS G12S
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Lumakras (sotorasib) • Krazati (adagrasib)
8ms
Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases. (PubMed, ESMO Open)
In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS G12R • KRAS G12A • KRAS G12 • KRAS G12S • KRAS Q61H • KRAS A146T • KRAS A146V • KRAS G13A • KRAS G13C
10ms
Application of plasma circulating KRAS mutations as a predictive biomarker for targeted treatment of pancreatic cancer. (PubMed, Cancer Sci)
Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12S
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Lumakras (sotorasib)
1year
RAS mutation specific survival in patients with metastatic colorectal cancer treated with trifluridine/tipiracil. (ASCO-GI 2024)
We did not confirm the negative predictive value of KRAS G12 mutation in patients treated with T/T, however, OS depends on the specific G12 mutation. In contrast, patients with KRAS G13 mutation had worse survival.
Clinical • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus)
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KRAS mutation • KRAS G12C • BRAF mutation • KRAS G12D • KRAS G12V • RAS mutation • RAS wild-type • KRAS G12A • KRAS G12 • KRAS G12S • KRAS G13
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Lonsurf (trifluridine/tipiracil)
1year
AMPLIFY-7P: Phase 1 and randomized phase 2 study of amphiphile immunotherapy ELI-002 7P as adjuvant treatment for subjects with G12D, G12R, G12V, G12C, G12A, G12S and G13D Kirsten rat sarcoma (KRAS)-mutated pancreatic ductal adenocarcinoma. (ASCO-GI 2024)
ELI-002 2P is a lymph node targeted immunotherapy comprised of Amphiphile (Amph)-modified G12D, G12R, G12V, G12C, G12A, G12S and G13D mutant KRAS peptides together with an Amph-modified CpG oligonucleotide adjuvant...Subsequent patients will receive up to 10 doses of Amph-peptides 7P 700 mcg each (4.9 mg total), together with Amph-CpG-7909 (10.0 mg) administered over a five-month treatment period...An interim analysis is planned using group sequential design for control of overall alpha 0.10. Clinical trial information: NCT05726864.
P1 data • P2 data • Preclinical • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • CA 19-9 (Cancer antigen 19-9)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12 • KRAS G12S • KRAS G13
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ELI-002 7P • Promune (agatolimod)
1year
PHRF1 Promotes Cell Invasion by Modulating SOX4 Expression in Colorectal Cancer HCT116-p53 Cells. (PubMed, Anticancer Res)
This study sheds light on the role of PHRF1 in the invasion of colorectal cancer HCT116-p53 cells, which harbor the oncogenic KrasG13D mutation and lack p53. These findings provide novel insights regarding the role of PHRF1 in invasion by modulating SOX4 expression in colorectal cancer HCT116-p53 cells.
Journal
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KRAS (KRAS proto-oncogene GTPase) • TGFB1 (Transforming Growth Factor Beta 1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • SOX4 (SRY-Box Transcription Factor 4)
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TP53 mutation • KRAS mutation • TP53 wild-type • KRAS G13D • KRAS G12 • KRAS G12S • TP53 expression • ZEB1 expression
1year
CRISPR-mediated reversion of oncogenic KRAS mutation results in increased proliferation and reveals independent roles of Ras and mTORC2 in the migration of A549 lung cancer cells. (PubMed, Mol Biol Cell)
Recently, others and we have shown that the mechanistic Target of Rapamycin Complex 2 (mTORC2) is a Ras effector in Dictyostelium and mammalian cells...Interestingly, our results suggest that K-Ras and mTORC2 promote A549 cell migration but as part of different pathways and independently of Ras's mutational status. Moreover, further characterization of the A549 cells revealed that loss of mutant K-Ras expression for the wild-type protein leads to an increase in cell growth and proliferation, suggesting that the A549 cells have low KRAS mutant dependency and that recovering expression of wild-type K-Ras protein increases these cells tumorigenic potential.
Journal
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KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)
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KRAS mutation • KRAS wild-type • RAS mutation • KRAS G12 • KRAS G12S • MTOR mutation • KRAS expression
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sirolimus
1year
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
1year
Title , Early Identification of KRAS and PIK3CA Mutations Using Multiplex Digital PCR Compatible with Liquid Biopsy Samples to Support Tumor Progression Surveillance (AMP 2023)
We developed a comprehensive multiplex mutant detection method with high sensitivity and specificity. This study demonstrates the strong potential of Absolute Q dPCR as a powerful multiplex platform for early mutation detection and monitoring in liquid biopsy samples.
Liquid biopsy • Biopsy
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KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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KRAS mutation • KRAS G12C • PIK3CA mutation • KRAS G12D • PIK3CA H1047R • KRAS wild-type • PIK3CA E545K • RAS wild-type • KRAS G12 • PIK3CA E542K • KRAS G12S • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + KRAS mutation
1year
Correlation between KRAS Mutation and CTLA-4 mRNA Expression in Circulating Tumour Cells: Clinical Implications in Colorectal Cancer. (PubMed, Genes (Basel))
These findings imply the genetic basis of KRAS with immunotherapeutic target molecules based on a real-time platform. This study also suggests the highly heterogeneous nature of cancer cells, which may facilitate the assessment of clonal dynamics across a single patient's disease.
Journal • Circulating tumor cells • IO biomarker • Tumor cell
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KRAS (KRAS proto-oncogene GTPase) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS G12A • KRAS G12 • KRAS G12S • CTLA4 expression • KRAS G13A • KRAS expression
1year
Characteristics and prognostic analysis of patients with detected KRAS mutations in resected lung adenocarcinomas by peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method. (PubMed, Transl Lung Cancer Res)
"Recently, sotorasib was developed as a molecular targeted drug for KRAS mutations...By the PNA-LNA PCR clamp method, G12C mutation of surgical specimens was detected successfully. The PNA-LNA PCR clamp method is expected to be applied to the detection of druggable G12C mutations."
Journal
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase)
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PD-L1 expression • KRAS mutation • KRAS G12D • KRAS G12V • ALK mutation • KRAS G12A • KRAS G12 • KRAS G12S
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therascreen® KRAS RGQ PCR Kit
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Lumakras (sotorasib)
1year
Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition. (PubMed, ACS Pharmacol Transl Sci)
The circumvention of gefitinib resistance by flunarizine was further demonstrated in an EGFR TKI (erlotinib)-refractory patient-derived tumor xenograft (PDX) model in vivo. Importantly, flunarizine was also shown to significantly potentiate the tumor growth suppressive effect of gefitinib in EGFR TKI-refractory PDX in vivo. The findings advocate for the translational application of flunarizine to circumvent gefitinib resistance in the clinic.
Journal • IO biomarker • Epigenetic controller
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KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDH1 (Cadherin 1) • BCL2L11 (BCL2 Like 11) • VIM (Vimentin) • E2F1 (E2F transcription factor 1)
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MET amplification • EGFR T790M • KRAS G12 • KRAS G12S • EGFR H1975 • VIM expression
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erlotinib • gefitinib
over1year
Cellular responses after (neratinib plus pemetrexed) exposure in NSCLC cells. (PubMed, Anticancer Drugs)
These findings argue against the development of 'early' resistance mechanisms after neratinib and pemetrexed exposure. Future studies will be required to understand how NSCLC cells become resistant to neratinib and pemetrexed.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • MCL1 (Myeloid cell leukemia 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • BCL2L1 (BCL2-like 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • ATG5 (Autophagy Related 5) • BECN1 (Beclin 1)
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KRAS G12C • NRAS mutation • EGFR L858R • HER-2 expression • EGFR T790M • EGFR expression • KRAS G12V • KRAS wild-type • RAS mutation • RAS wild-type • NRAS Q61K • KRAS G12A • KRAS G12 • NRAS Q61 • KRAS G12S • KRAS Q61H • MCL1 expression • NRAS G12 • KRAS Q61K • NRAS G12S
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Nerlynx (neratinib) • pemetrexed
over1year
Evaluation of the Prognostic Value of Low-Frequency KRAS Mutation Detection in Circulating Tumor DNA of Patients with Metastatic Colorectal Cancer. (PubMed, J Pers Med)
Re-challenge therapy with a combination of anti-EGFR, anti-VEGF, and FOLFIRI chemotherapy was found to be ineffective in a patient with 0.38% KRAS G12D mutation in baseline ctDNA. Our study suggests that the detection of low-frequency KRAS mutations in ctDNA could be used as a predictor of treatment response in mCRC patients.
Journal • Circulating tumor DNA • Metastases
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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TP53 mutation • KRAS mutation • KRAS G12D • KRAS G12V • APC mutation • KRAS G12 • KRAS G12S • KRAS G13
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5-fluorouracil • irinotecan • leucovorin calcium
over1year
Next-generation sequencing enables identification of RET rearrangements in papillary thyroid cancer (ESMO 2023)
Conclusions Molecular screening in non-BRAF PTC patients is useful to identify patients harboring RET fusions who may benefit from targeted therapies. As other potentially actionable gene fusions are also found in these patients, routine implementation of NGS analysis warrants a comprehensive biomarker study.
Next-generation sequencing
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • TERT (Telomerase Reverse Transcriptase) • CCDC6 (Coiled-Coil Domain Containing 6) • ETV6 (ETS Variant Transcription Factor 6) • STRN (Striatin) • NCOA4 (Nuclear Receptor Coactivator 4)
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BRAF V600E • KRAS mutation • BRAF V600 • RET fusion • RET rearrangement • KRAS G12 • NRAS Q61 • KRAS G12S • NRAS Q61R • NCOA4-RET fusion • TERT mutation • TERT promoter mutation • NRAS G12S • RET expression
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Idylla™ GeneFusion Assay • Oncomine Focus Assay
over1year
Impact of co-mutations on the prognosis of targeted therapy in EGFR-mutant advanced NSCLC: A result of real-world study (ESMO 2023)
Multifactorial analysis showed that TP53 mutation (HR 2.198, 95% CI 1.006-4.803; P = 0.048) and RB1 mutation (HR 8.798, 95% CI 1.604-48.269; P = 0.012) were independent risk factors for PFS with first-line targeted therapy. Conclusions This research added to the evidence that co-alterations such as TP53, MET, and RB1 are prospective prognostic biomarkers in NSCLC patients treated with EGFR-TKI.
Clinical • Real-world evidence • Real-world • Metastases
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1)
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TP53 mutation • KRAS mutation • EGFR mutation • PIK3CA mutation • EGFR amplification • PIK3CA H1047R • KRAS G12V • DNMT3A mutation • PIK3CA E545K • RB1 mutation • KRAS G12 • KRAS G12S • EGFR mutation + PIK3CA mutation • PIK3CA E545
over1year
Prognostic value of KRAS and BRAF mutations in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: An ACCENT/IDEA pooled analysis of 7 trials (ESMO 2023)
Conclusions In the largest analysis of the association of KRAS exon 2 and BRAFV600E mutations and disease outcome in resected stage III CC, either mutation was associated with significantly shorter DFS, OS and SAR in MSS tumors, but only with shorter SAR in MSI-H tumors. In addition, all KRAS codon 12 and 13 mutations had similar prognostic value.
Retrospective data • MSi-H Biomarker
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)
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BRAF V600E • KRAS mutation • MSI-H/dMMR • KRAS G12C • BRAF mutation • BRAF V600 • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12 • KRAS G12S • KRAS exon 2 mutation
over1year
Impact of Co-mutations on the Prognosis of Targeted Therapy in EGFR-Mutant Advanced NSCLC: a Result of Real-World Study (IASLC-WCLC 2023)
This research added to the evidence that co-alterations such as TP53, MET, and RB1 are prospective prognostic biomarkers in NSCLC patients treated with EGFR-TKI.
Clinical • Real-world evidence • Real-world • Metastases
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1)
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TP53 mutation • KRAS mutation • EGFR mutation • PIK3CA mutation • EGFR amplification • PIK3CA H1047R • KRAS G12V • DNMT3A mutation • PIK3CA E545K • RB1 mutation • KRAS G12 • KRAS G12S • EGFR mutation + PIK3CA mutation • PIK3CA E545
over1year
Clinical Impact of Next-Generation Sequencing in KRAS-Mutated Non-Small Cell Lung Cancer Patients: a Single-Center Experience (IASLC-WCLC 2023)
The clinicopathological characteristics of included patients were consistent with the published literature. In the majority of KRAS-mutated patients included in this study, the use of NGS allowed for the detection of additional genetic alterations with potential clinical significance.
Clinical • Next-generation sequencing • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12 • KRAS G12S • KRAS G13 • KRAS G13C
over1year
Histone deacetylase inhibitor belinostat regulates metabolic reprogramming in killing KRAS-mutant human lung cancer cells. (PubMed, Mol Carcinog)
Another HDACi panobinostat also showed potential anticancer effect in both H358 and A549 cells via Nrf2 pathway. In summary, belinostat is effective in killing KRAS-mutant human lung cancer cells by regulating mitochondrial metabolism which could be used as biomarkers for preclinical and clinical studies.
Journal • Epigenetic controller
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KRAS (KRAS proto-oncogene GTPase) • NQO1 (NAD(P)H dehydrogenase, quinone 1)
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KRAS mutation • KRAS G12C • KRAS G12 • KRAS G12S
|
Farydak (panobinostat) • Beleodaq (belinostat)
over1year
RAS-mutations in population-based and real-life metastatic colorectal cancer cohorts (ESMO-GI 2023)
In this cohort with population-based and real-world patients, no differences in patient characteristics or treatment modalities were seen between different RAS mt, except a higher frequency of right-colon primaries among KRAS mt compared with NRAS mt. KRAS -G12S conferred a worse OS compared with some other KRAS mt, whereas no other differences in OS were seen. It therefore seems as if different RAS mt behave quite similar.
Clinical • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
|
BRAF V600E • KRAS mutation • KRAS G12C • NRAS mutation • BRAF V600 • KRAS G12D • KRAS G12V • RAS mutation • NRAS Q61K • KRAS G12A • KRAS G12 • NRAS Q61 • KRAS G12S • NRAS Q61R • KRAS G13 • KRAS Q61H • NRAS G12D • NRAS G12 • NRAS G13 • KRAS A146T • NRAS A146T • NRAS A146 • KRAS G12C + KRAS G12V • KRAS Q61K • NRAS G12S
over1year
RAS/ BRAF molecular profile in metastatic versus non-metastatic colorectal cancer (ESMO-GI 2023)
Our results highlighted a difference in the molecular profile of KRAS, NRAS,and BRAF mutations' distribution between metastatic colorectal cancer and non-metastatic ones: NRAS and BRAF mutations were associated with metastasis advent; moreover, the G13D mutation of KRAS was correlated to a better prognosis than mutations in codon 12 of KRAS: G12A and G12S alleles gave the worst prognosis.
Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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KRAS mutation • BRAF mutation • NRAS mutation • KRAS G12D • KRAS G12V • RAS mutation • KRAS G12A • KRAS G12 • KRAS G12S • KRAS G13 • NRAS G12D • NRAS G13 • NRAS G12S
|
Idylla™ KRAS Mutation Test • Idylla™ NRAS-BRAF Mutation Test
over1year
The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer. (PubMed, Oncologist)
These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.
Journal • Metastases
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12 • KRAS G12S
|
Avastin (bevacizumab)
over1year
Comprehensive genomic profiling of tumor tissue and plasma-circulating tumor DNA in RAS/BRAFV600E wild type metastatic colorectal cancer patients: Initial findings from the CAPRI 2-GOIM trial (ESMO-GI 2023)
P2 | "According to liquid biopsy before second- and third-line therapies, treatment sequences are: FOLFIRI + cetuximab (first-line), FOLFOX + cetuximab (second-line); irinotecan + cetuximab (third-line) in patients with plasma ctDNA RAS/BRAFV600E WT tumors. In patients with RAS/BRAFV600E mutant tumors, second-line is FOLFOX + bevacizumab, while third-line is regorafenib or trifluridine/tipiracil (investigator's choice)... Both tumor tissue- and liquid biopsy-based comprehensive genomic profiling by NGS identify additional molecular alterations, that could be involved in resistance to anti-EGFR monoclonal antibodies, as compared to PCR-based tumor tissue analysis. CAPRI 2-GOIM trial will determine if NGS would allow better selection of RAS/BRAFV600E WT mCRC patients for the most appropriate treatments through three sequential lines of therapies."
Clinical • Circulating tumor DNA
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • SMAD4 (SMAD family member 4) • RAS (Rat Sarcoma Virus)
|
TP53 mutation • BRAF V600E • KRAS mutation • KRAS G12C • HER-2 amplification • NRAS mutation • BRAF V600 • KRAS G12V • BRAF wild-type • RAS mutation • NRAS Q61K • KRAS G12 • NRAS Q61 • BRAF fusion • KRAS G12S • BRAF K601E • NRAS G12 • NRAS G13 • KRAS A146T • NRAS A146T • NRAS G13D • NRAS A146 • BRAF amplification • NRAS G12V • BRAF K601
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FoundationOne® CDx • FoundationOne® Liquid CDx
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Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • Stivarga (regorafenib) • irinotecan • Lonsurf (trifluridine/tipiracil) • leucovorin calcium
over1year
RAS gene mutations and histomorphometric measurements in oral squamous cell carcinoma. (PubMed, Biotech Histochem)
Our findings suggest that KRAS may be mutated more frequently in OSCC compared to HRAS and NRAS. Also, the histological features of nuclear and cellular diameter differed significantly between the KRAS mutated and unmutated cases.
Journal
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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KRAS mutation • RAS mutation • HRAS mutation • NRAS Q61 • KRAS G12S • KRAS Q61H • NRAS G12 • NRAS Q61L • HRAS Q61L • HRAS G12S • KRAS Q61L • NRAS G12S
over1year
Osimertinib and selpercatinib efficacy, safety, and resistance in a multicenter, prospectively treated cohort of EGFR-mutant and RET fusion-positive lung cancers. (PubMed, Clin Cancer Res)
For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible, safe, and offered clinical benefit, supporting the prospective evaluation of this combination.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • EML4 (EMAP Like 4) • KIF5B (Kinesin Family Member 5B) • CCDC6 (Coiled-Coil Domain Containing 6) • STRN (Striatin) • NCOA4 (Nuclear Receptor Coactivator 4)
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BRAF V600E • EGFR mutation • BRAF V600 • EGFR exon 19 deletion • EGFR T790M • RET fusion • EGFR C797S • RET mutation • KRAS G12 • KRAS G12S • NCOA4-RET fusion • RET positive
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Tagrisso (osimertinib) • Retevmo (selpercatinib)
almost2years
A Novel Combination of Sotorasib and Metformin Enhances Cytotoxicity and Apoptosis in KRAS-Mutated Non-Small Cell Lung Cancer Cell Lines through MAPK and P70S6K Inhibition. (PubMed, Int J Mol Sci)
Furthermore, we observed a synergic effect on cytotoxicity and apoptosis induction, as well as a notable inhibition of the MAPK and AKT-mTOR pathways after treatment with the combination, predominantly in KRAS-mutated cells (H23 and A549). The combination of metformin with sotorasib synergistically enhanced cytotoxicity and apoptosis induction in lung cancer cells, regardless of KRAS mutational status.
Preclinical • Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS wild-type • RAS mutation • RAS wild-type • KRAS G12 • KRAS G12S
|
Lumakras (sotorasib) • metformin
almost2years
Sotorasib and metformin combination enhances cytotoxicity and apoptosis in KRAS mutant lung cancer cell lines (AACR 2023)
The combination of metformin with sotorasib showed synergic effects on cytotoxicity, increased apoptosis induction, and a remarkable inhibition of downstream proteins involved in the signaling of growth factor receptors in all tested cells. Moreover, these results suggest a sensitizing effect of metformin to sotorasib treatment in cells without KRAS mutations, such as H522.
Preclinical
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KRAS (KRAS proto-oncogene GTPase) • RPS6KB1 (Ribosomal Protein S6 Kinase B1) • ANXA5 (Annexin A5)
|
KRAS mutation • KRAS G12C • KRAS G12S
|
Lumakras (sotorasib) • metformin
almost2years
Circumvention of gefitinib resistance by repurposing flunarizine via histone deacetylase inhibition in lung cancer (AACR 2023)
To this end, unlike the control HDACI vorinostat, flunarizine (tested at the resistance circumventing concentrations) did not appreciably affect acetylation of representative non-histone proteins (including α-tubulin and p53) relevant to drug resistance. The findings advocate further clinical evaluation of the repurposing use of flunarizine to overcome gefitinib resistance.
IO biomarker • Epigenetic controller
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KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDH1 (Cadherin 1) • BCL2L11 (BCL2 Like 11) • VIM (Vimentin) • E2F1 (E2F transcription factor 1)
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EGFR mutation • MET amplification • EGFR T790M • KRAS G12 • KRAS G12S • CDH1 expression • EGFR H1975 • VIM expression
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gefitinib • Zolinza (vorinostat)
almost2years
KRAS Mutational Profiles among Colorectal Cancer Patients in the East Coast of Peninsular Malaysia. (PubMed, Diagnostics (Basel))
Current analyses revealed that a significant proportion of CRC patients in the East Coast of Peninsular Malaysia have KRAS mutations, where this frequency is higher compared to those in the West Coast. The findings of this study would serve as a precursor for further research that explores KRAS mutational status and the profiling of other candidate genes among Malaysian CRC patients.
Journal
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KRAS (KRAS proto-oncogene GTPase) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12 • KRAS G12S