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KRAS (KRAS proto-oncogene GTPase)

News alerts, weekly reports and conference planners

AMG 510 Ethnic Sensitivity Study (CodeBreaK 105). (clinicaltrials.gov)

P1, N=12, Active, not recruiting, Amgen | Trial completion date: Dec 2024 --> Jun 2025

1 day ago

Trial completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Lumakras (sotorasib)

RMC-6236-001: Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS (clinicaltrials.gov)

P1, N=614, Recruiting, Revolution Medicines, Inc. | Trial completion date: Dec 2025 --> Jun 2026

1 day ago

Trial completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • RAS mutation • KRAS G12

RMC-6236

KontRASt-02: Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)

P3, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2024 --> May 2025

1 day ago

Trial primary completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

docetaxel • opnurasib (JDQ443)

Diagnostic and Clinical Utility of OncoScan Microarray and NGS-Based Sequencing in Pediatric Solid Tumors: Children's Mercy Hospital Experience (AMP 2024)

OS+ is a reliable test to identify clinically relevant genomic alterations, cnLOH, and several hotspot mutations in pediatric FFPE solid tumor specimens. WGS/WES significantly increases the yield of actionable somatic mutations and cancer-predisposing germline variants. The cost, turnaround time, and tumor percentage in the specimen make OS+ followed by WES principal tests for pediatric solid tumor analysis at our institution.

2 days ago

Clinical • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • H3-3A (H3.3 Histone A)

TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • PIK3CA mutation • BRAF V600 • PTEN mutation • BRAF fusion

OncoScan™ CNV Assay

IDH1/2 Mutations in Lung Cancer: A Closer Look at Their Incidence, Origin, and Clinical Characteristics (AMP 2024)

IDH1/2 mutations are identified in a small subset of NSCLCs. Our findings suggest that >25% of these mutations are hematopoietic in origin with important implications for diagnosis and management of these patients. Among those with mutations arising from the lung neoplasm, IDH1/2 mutations were primarily seen in conjunction with another driver and were subclonal in nature, suggesting patterns of clonal heterogeneity and evolution.

2 days ago

Clinical • Tumor mutational burden

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

KRAS mutation • BRAF mutation • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH1 R132L • IDH2 R140 • IDH2 R172

MSK-IMPACT

Actionable Mutation Profiling in Solid Tumours in Australia Using Targeted Next-Generation Sequencing Panel (AMP 2024)

We demonstrated the feasibility of obtaining actionable information within a clinically meaningful turnaround time using a robust NGS solution. For samples with sufficient tumour content and DNA for testing (>90% of samples), Find It had an approximately 99% success rate. Actionable information provided by the panel could impact clinical management for 66% of advanced-stage cancer patients.

2 days ago

Next-generation sequencing

KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • RAS mutation • EGFR positive

Find It®

Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)

Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.

2 days ago

Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion

OncoExTra™ test

Characterization of Signaling Pathways in Solid Tumors Using Comprehensive Genomic Profiling (AMP 2024)

Growth and proliferation pathways are altered more in certain cancers than in others; however, the CC pathway is altered to a lesser extent but across cancers. The HRR pathway is predominantly altered in ovarian and prostate cancers. RTK/Ras and PI3K pathways have been well studied with smaller panels and established genes; however, large panels allow for inclusion of additional components of these pathways, and assessment of HRR and CC pathways more effectively.

2 days ago

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • FGFR1 (Fibroblast growth factor receptor 1) • HRD (Homologous Recombination Deficiency)

KRAS mutation

TruSight Oncology 500 Assay

Clinical Verification of an FDA-Approved Solid Tumor IVD Assay (AMP 2024)

As with all assays, this test has its benefits and limitations. A primary benefit is the speed and relative ease of performance. Library preparation is scalable for 6 to 48 samples and can be completed in a day.

2 days ago

Clinical

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)

Pan-cancer OncoReveal™ CDx

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.

2 days ago

Next-generation sequencing

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

Low Limit of Detection Increases Detection and Reporting of Actionable Genomic Alterations (AMP 2024)

The ability to detect SNVs and indels below 5% VAF increases the diagnostic yield of actionable genomic alterations. This enables additional patients to consider FDA-approved on-label targeted therapies as a treatment option. Taken together, CGP assays that couple high sensitivity and low LOD can maximize identification of therapeutically relevant alterations across solid tumor types.

2 days ago

BRCA Biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600 • PTEN mutation

OncoExTra™ test

Clinical Validation of an Amplicon-Based Next-Generation Sequencing (NGS) Liquid Biopsy Assay for Predictive Testing in Patients with Solid Tumours (AMP 2024)

The assay shows good performance in detecting hotspot SNVs and small indels in ctDNA, and is suitable for clinical use. The limitation of bioinformatics pipelines in variant calling should be noted, and consideration can be given to run multiple pipelines in parallel to avoid missing out variants.

2 days ago

Clinical • Liquid biopsy • Next-generation sequencing • Biopsy

EGFR exon 20 insertion • EGFR exon 20 mutation

Oncomine™ Pan-Cancer Cell-Free Assay

Detection of Novel Fusion Events in Gastric Carcinoma Involving the ARHGAP Gene Family (AMP 2024)

Our study documents novel fusions in MSS gastric carcinoma involving the ARHGAP family. Patients with these tumors usually lack eligibility for targeted therapies, such as those directed against HER2 and involving immune checkpoint inhibition, and could ultimately benefit from new treatment avenues modulating RHOA activity as a result of ARHGAP fusions.

2 days ago

Tumor mutational burden • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • CLDN18 (Claudin 18) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KDM6A (Lysine Demethylase 6A) • RHOA (Ras homolog family member A) • SOX9 (SRY-Box Transcription Factor 9) • ELF3 (E74 Like ETS Transcription Factor 3) • ARHGAP • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CTNND1 (Catenin Delta 1) • ARHGAP42 (Rho GTPase Activating Protein 42)

TMB-H • HER-2 amplification • PBRM1 mutation

MI Tumor Seek™

Same-Day Molecular Testing Results from Cytology Specimens: The Next Frontier of the Rapid On-Site Evaluation? (AMP 2024)

It is feasible to yield actionable molecular testing results from cytology specimens within 2 to 3 hours of the patient's diagnostic procedure, and aspirate smears can be triaged for this use at the time of the rapid on-site evaluation. Targetable genetic alterations can be detected from destained cytology aspirate smear slides and unstained FFPE cell blocks with high accuracy, precision, and analytical sensitivity and specificity. The cost of each cartridge ranges from $127 to $462 and is covered by the average national reimbursement schemes.

2 days ago

Cytology

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)

ALK rearrangement • RET rearrangement

Idylla™ KRAS Mutation Test

Rapid On-Site Next-Generation Sequencing (NGS) Testing as an Alternative to Single Gene or Send-Out Molecular Testing in Lung and Colon Cancers (AMP 2024)

Given the importance of timely, comprehensive molecular test results to inform appropriate treatment decisions in NSCLC and CRC, these results suggest that the rapid in-house GeneXus NGS system can reduce TAT with comparable failure rates and alteration detection rates compared to other testing methods. Further studies evaluating the impact of the rapid OPA compared to other methods on patient care, as well as the economics of different molecular tests, are ongoing.

2 days 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) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

KRAS G12C • KRAS G12

Oncomine Precision Assay

DNA and RNA NGS for Myeloid Neoplasms Using Oncomine Myeloid Assay GX v2 on GeneXus: An Assessment of Clinical Utility (AMP 2024)

This DNA- and RNA-based 80-gene panel has proven to be a powerful tool for genomic profiling of myeloid neoplasms. The results were provided to hematopathologists/oncologists in timely fashion with the critical information for diagnosis confirmation, and disease classification, as well as assessment of patient response to treatment.

2 days ago

Clinical • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

FLT3-ITD mutation • NPM1 mutation • U2AF1 mutation • CEBPA mutation • JAK2 V617F

Oncomine Myeloid Assay GX

Twelve-Month Retrospective Evaluation of Clinical Whole-Exome Sequencing (WES) Results for Indolent B Cell Lymphomas (AMP 2024)

Our NGS testing found tier 1 or 2 variants in the majority of cases, supporting its use in the clinical setting. Additionally, a subset of variants identified with the pan-Heme list likely represents mutations of clonal hematopoiesis of indeterminate potential, which could be removed with a more lymphoma-specific gene list. Given these findings, and a growing number of targets in indolent B cell lymphomas, future studies focusing on evaluation of a lymphoma-specific gene list is of interest for clinical validation and implementation.

2 days ago

Retrospective data • Whole exome sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein)

FusionPlex™ Pan-Heme panel • PanHeme assay

A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors (clinicaltrials.gov)

P1, N=750, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

3 days ago

Enrollment open

KRAS (KRAS proto-oncogene GTPase)

Keytruda (pembrolizumab) • Erbitux (cetuximab) • cisplatin • carboplatin • gemcitabine • albumin-bound paclitaxel • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium

BREATHE: Prospective, Longitudinal Biocollection in Thoracic Oncology, Including Newly Diagnosed Lung Cancer Patients (clinicaltrials.gov)

P=N/A, N=730, Not yet recruiting, Nantes University Hospital | Trial completion date: Sep 2034 --> Dec 2034 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2029 --> Dec 2029

3 days ago

Trial completion date • Trial initiation date • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation

EXCALIBUR3: EXtended CriteriA Treatment for LIver Metastases and Heavy Tumour BURden (clinicaltrials.gov)

P2, N=62, Suspended, Oslo University Hospital | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024

3 days ago

Trial suspension • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)

KRAS mutation • BRAF mutation

Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients (clinicaltrials.gov)

P1/2, N=85, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Dec 2024

3 days ago

Enrollment closed • Trial primary completion date • Combination therapy

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation

Krazati (adagrasib) • avutometinib (VS-6766)

A prospective clinical study to evaluate the efficacy of dexitabine in maintenance therapy after hematopoietic stem cell transplantation in juvenile myelomonocytic leukemia (ChiCTR2400091166)

P=N/A, N=40, Not yet recruiting, The Seventh Affiliated Hospital, Sun Yat-sen University; The Seventh Affiliated Hospital, Sun Yat-sen University

5 days ago

New trial

KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

KRAS mutation • NRAS mutation • NF1 mutation • PTPN11 mutation • CBL mutation

The safety and efficacy of fruquintinib combined with standard chemotherapy and cadonilimab for second-line treatment of advanced colorectal cancer: A single-arm, prospective, exploratory clinical study (ChiCTR2400091176)

P2, N=58, Not yet recruiting, Xuancheng People's Hospital; Xuancheng People's Hospital of Anhui Province

5 days ago

New P2 trial • Metastases

KRAS (KRAS proto-oncogene GTPase)

KRAS wild-type • RAS wild-type

Fruzaqla (fruquintinib) • Kaitanni (cadonilimab)

HRS-4642 combined with gemcitabine and albumin-bound paclitaxel for neoadjuvant and adjuvant treatment of pancreatic cancer: an xploratory clinical study. (ChiCTR2400089937)

P2, N=20, Not yet recruiting, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

5 days ago

New P2 trial

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12D • KRAS G12

gemcitabine • albumin-bound paclitaxel • HRS-4642

Phase I/IIa Study evaluating the safety, tolerability, pharmacokinetics, and efficacy of DN022150 in patients with advanced solid tumors Harboring KRASG12D mutation (ChiCTR2400088951)

P1/2, N=181, Not yet recruiting, Zhongshan Hospital ,Fudan University; Zhongshan Hospital ,Fudan University

5 days ago

New P1/2 trial • Metastases

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12D • KRAS G12

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Profiles, and Preliminary Efficacy of SYS6023 in Patients with Advanced Solid Tumors (ChiCTR2400089836)

P1, N=388, Recruiting, Shanghai Chest Hospital; CSPC Megalith Biopharmaceutical Co., Ltd

5 days ago

New P1 trial • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • HER-2 negative • BRAF V600 • HER-2 expression • ALK positive • MET amplification • ALK fusion • ERBB3 expression • RET mutation • ROS1 fusion • MET mutation • NRG1 fusion • RET rearrangement • KRAS G12 • KRAS amplification • ER expression • PGR expression • ALK-ROS1 fusion • NRG1 fusion • NTRK fusion

An open, multicentre, phase I/II study to evaluate the effectiveness and safety of IBI351 combined with platinum-containing chemotherapy and ⻉vazumab in subjects of KRAS G12C mutation or metastatic non-squamous non-small cell lung cancer subjects (ChiCTR2400090974)

P1/2, N=28, Not yet recruiting, HenanCancerHospital; HenanCancerHospital

5 days ago

New P1/2 trial • Metastases

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Dupert (fulzerasib)

CodeBreaK 201: A Study of Sotorasib (AMG 510) in Participants With Stage IV NSCLC Whose Tumors Harbor a KRAS p.G12C Mutation in Need of First-line Treatment (clinicaltrials.gov)

P2, N=42, Active, not recruiting, Amgen | Trial completion date: Nov 2024 --> Jan 2026 | Trial primary completion date: Nov 2024 --> Jan 2026

7 days ago

Trial completion date • Trial primary completion date • Metastases

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)

KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12

Lumakras (sotorasib)

Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC. (PubMed, JTO Clin Res Rep)

Overall, both existing literature and our data suggest that RET-FISH testing can be used for rapid screening of RET rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm RET-FISH-positive cases is essential for ensuring that only patients likely to benefit from RET-target therapy receive the treatment.

8 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

RET rearrangement

SWItch/Sucrose Nonfermentable complex-deficient pulmonary neoplasms: clinicopathologic characteristics and outcomes to radiotherapy and immunotherapy. (PubMed, Transl Lung Cancer Res)

SWI/SNF-d pulmonary neoplasms, whether with multiple or single subunit losses, exhibit similar clinicopathological characteristics. Radiotherapy and immunotherapy are effective treatments for these patients, and the combination of radiotherapy with immunotherapy may offer synergistic effects.

8 days ago

Journal • IO biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)

KRAS mutation • STK11 mutation

KRAS inhibitors in drug resistance and potential for combination therapy. (PubMed, Tumori)

Recently, an emergency approval from the US-FDA has been issued for KRASG12C inhibitors (sotorasib and adagrasib) for metastatic lung cancer treatment. Moreover, because KRASG12D and KRASG12V are more common than KRASG12C, focus must be placed on the therapeutic strategies for this type of patient, along with sustained efforts in research on these targets. In the present review, we try to focus on various strategies to overcome rapid resistance through the use of combinational treatments to improve the activity of KRASG12C inhibitors.

8 days ago

Review • Journal • Combination therapy

KRAS (KRAS proto-oncogene GTPase)

KRAS G12D • KRAS G12V

Lumakras (sotorasib) • Krazati (adagrasib)

CIFRA: Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients (clinicaltrials.gov)

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Sep 2024 --> Sep 2025

8 days ago

Trial completion date • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD163 (CD163 Molecule) • GZMB (Granzyme B) • TGFB1 (Transforming Growth Factor Beta 1) • FOXP3 (Forkhead Box P3) • CD86 (CD86 Molecule)

KRAS wild-type • BRAF wild-type • NRAS wild-type • CD163 expression

Erbitux (cetuximab) • 5-fluorouracil • irinotecan

Dependence of NPPS creates a targetable vulnerability in RAS-mutant cancers. (PubMed, Acta Pharmacol Sin)

Pharmacological inhibition of NPPS-HK1 axis using NPPS inhibitor Enpp-1-IN-1 or HK1 inhibitor 2-deoxyglucose (2-DG), or genetic interfere with NPPS suppressed RAS-mutant cancers in vitro and in vivo. In conclusion, this study reveals an unrecognized mechanism and druggable lynchpin for modulation of pan-mutant-RAS pathway, proposing a new potential therapeutic approach for treating RAS-mutant cancers.

8 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)

KRAS mutation • RAS mutation • RAS wild-type

KRAS and EGFR inhibitors: a new step in the management of colorectal cancer. (PubMed, Transl Gastroenterol Hepatol)

No abstract available

9 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

Vectibix (panitumumab) • Lumakras (sotorasib) • Krazati (adagrasib)

Precision medicine in metastatic colorectal cancer: targeting KRAS G12C mutation. (PubMed, Transl Gastroenterol Hepatol)

No abstract available

9 days ago

Journal • Metastases

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

KRAS G12C inhibitors in metastatic colorectal cancer: a tale of two targets. (PubMed, Transl Gastroenterol Hepatol)

No abstract available

9 days ago

Journal • Metastases

KRAS (KRAS proto-oncogene GTPase)

Adagrasib in KRYSTAL-12 has Broken the KRAS G12C Enigma Code in Non-Small Cell Lung Carcinoma. (PubMed, Lung Cancer (Auckl))

The Phase III KRYSTAL-12 trial demonstrated that adagrasib significantly improved median progression-free survival (mPFS) compared with docetaxel (HR, 0.58; 95% CI: 0.45-0.76; P<0.0001) and increased the intracranial objective response rate (ORR) to 40% in the central nervous system (CNS) evaluable population. This paper evaluates the clinical efficacy of adagrasib in KRAS G12C-mutated advanced NSCLC discussing its potential advantages over other inhibitors such as sotorasib. Despite not reaching the 6-month mPFS benchmark, adagrasib offers significant clinical benefits, particularly for the management of CNS metastases. In this pros and cons debate, we argue that adagrasib has broken the KRAS G12C enigma code in NSCLC.

9 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

docetaxel • Lumakras (sotorasib) • Krazati (adagrasib)

MGST1 facilitates novel KRASG12D inhibitor resistance in KRASG12D-mutated pancreatic ductal adenocarcinoma by inhibiting ferroptosis. (PubMed, Mol Med)

Our data showed that KRASG12D inhibitor MRTX1133 combined with PKF-118-310 could enhance the effectiveness of MRTX1133 treatment response through induction of ferroptosis via inhibiting MGST1 expression in MRTX1133-resistant PDAC cells and tumors. This evidence may provide a promising strategy to overcome KRASG12D inhibitor MRTX1133 resistance in PDAC patients with KRASG12D mutations.

9 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TCF4 (Transcription Factor 4)

KRAS mutation • KRAS G12D • CTNNB1 expression

MRTX1133

KRAS mutations in endometrial cancers: Possible prognostic and treatment implications. (PubMed, Gynecol Oncol)

KRAS-mut represents a genotypically distinct group of ECs. Overlap exists with genomic predictors (TMB-high, MSI-high) of immunotherapy response, suggesting a possible biomarker-driven combination option with immunotherapy. Clinical trials to evaluate these strategies should be developed.

9 days ago

Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability)

KRAS mutation • BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS overexpression • HER-2 positive + RAS wild-type

USP7 deubiquitinates KRAS and promotes non-small cell lung cancer. (PubMed, Cell Rep)

Moreover, USP7 inhibitors suppress NSCLC cell proliferation, particularly in cells resistant to the KRAS-G12C inhibitor AMG510. In conclusion, our findings identify USP7 as a key deubiquitinase regulating RAS stability, and targeting USP7 is a promising strategy to counteract KRAS inhibitor resistance in NSCLC.

9 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • USP7 (Ubiquitin Specific Peptidase 7)

KRAS mutation • RAS mutation

Lumakras (sotorasib)

10d

The potential role of next-generation sequencing in identifying MET amplification and disclosing resistance mechanisms in NSCLC patients with osimertinib resistance. (PubMed, Front Oncol)

The known resistance mechanisms, including MET amplification, EGFR (C797S, L718Q/R), TP53, CDK4, CDK6, CDKN2A, BRAF, KRAS, NRAS and PIK3CA mutations were also disclosed in our cohort. NGS assay can achieve a high concordance with FISH in MET amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion.

10 days ago

Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)

TP53 mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • MET amplification • EGFR T790M • EGFR C797S • EGFR L718Q • BRAF amplification • EGFR C797S + MET amplification

Tagrisso (osimertinib)

10d

Comprehensive liquid biopsy analysis for monitoring NSCLC patients under second-line osimertinib treatment. (PubMed, Front Oncol)

AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.

10 days ago

Journal • Liquid biopsy • PD(L)-1 Biomarker • IO biomarker • Biopsy

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) • MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase) • B2M (Beta-2-microglobulin) • FOXA1 (Forkhead Box A1) • PIM1 (Pim-1 Proto-Oncogene) • VIM (Vimentin) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • KRT19 (Keratin 19) • RASSF1 (Ras Association Domain Family Member 1) • WIF1 (WNT Inhibitory Factor 1) • BRMS1 (BRMS1 Transcriptional Repressor And Anoikis Regulator)

PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • MET amplification • EGFR T790M • MET mutation • KRAS G12 • EGFR mutation + PIK3CA mutation • HER-2 amplification + PD-L1 expression • VIM expression • HER-2 amplification + MET amplification • RASSF1 methylation

Tagrisso (osimertinib)