The "second chance" for FTIs is here but the successful clinical implementation of FTIs can only be achieved if the design of the new clinical trials do not repeat mistakes of the past: application of these drugs without predictive markers.

12 days ago

Review • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • HRAS (Harvey rat sarcoma viral oncogene homolog)

HRAS mutation

Zarnestra (tipifarnib)

13d

Study of Daraxonrasib (RMC-6236) in Patients With RAS Mutated NSCLC (RASolve 301) (clinicaltrials.gov)

P3, N=590, Recruiting, Revolution Medicines, Inc. | N=420 --> 590

13 days ago

Enrollment change

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

KRAS mutation • NRAS mutation • RAS mutation • HRAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS Q61

docetaxel • daraxonrasib (RMC-6236)

16d

The role of inflammation in the immune evasion of KRas. (PubMed, Front Immunol)

We review reports of the interaction of cathepsin B with trypsinogen in the pancreas and caspases in inflammasomes and the potential effect of premature activation of trypsin on immune evasion of G12R mutants. We summarize our observations and literature review in a schematic describing the potential role inflammation and the actions of cathepsin B, trypsin, and caspases on the immune evasion of KRas and related Ras family gene products.

16 days ago

Review • Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

KRAS mutation • NRAS mutation • HRAS mutation • KRAS G12 • KRAS G13 • NRAS G13

22d

19-C-0017: Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients (clinicaltrials.gov)

P1/2, N=5, Terminated, National Cancer Institute (NCI) | Completed --> Terminated; Study was closed due to lack of accrual and study outcomes overlapped with another protocol's eligibility.

22 days ago

Trial termination • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

PD-L1 expression • KRAS mutation • NRAS mutation • KRAS G12D • HRAS mutation • KRAS G12 • NRAS G12

cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)

24d

Urothelial Carcinoma in Children and Young Adults is Characterized by Higher Frequency of HRAS Mutations and Lower Prevalence of TERT Promoter and FGFR3 Mutations. (PubMed, Am J Surg Pathol)

FGFR3 mutation was not detected in any of the cases. Urothelial carcinomas occurring in children and young adults exhibit a distinct molecular profile compared with those in older patients, characterized by a higher frequency of HRAS mutations and a significantly lower prevalence of TERT promoter and FGFR3 alterations.

24 days ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase)

FGFR3 mutation • HRAS mutation

24d

HPV-Associated Sarcomatoid (Spindle Cell) Carcinoma of the Base of the Tongue with HRAS and TERT Promoter Mutations. (PubMed, Head Neck Pathol)

We report a rare case of HPV-associated sarcomatoid carcinoma of the base of the tongue. The predominance of spindle cell morphology combined with an atypical immunophenotype-lack of squamous markers and strong p16 expression-poses a significant diagnostic challenge, particularly in small biopsies. Comprehensive diagnostic evaluation, including HPV-specific testing such as in situ hybridization, is critical for accurate diagnosis.

24 days ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • MME (Membrane Metalloendopeptidase) • TP63 (Tumor protein 63)

HRAS mutation • NRAS G12

Sinonasal biphasic seromucinous adenocarcinomas: a report of two morphologically distinct cases with multimodal omics characterization. (PubMed, Virchows Arch)

One oncocytic case showed HRAS and AKT1 activating mutations; the other basaloid case had a FGFR2::SORB3 fusion. Spatial transcriptomics revealed divergent intra- and inter-tumoral signatures emphasizing the transcriptomic heterogeneity within biphasic components.

1 month ago

Journal

BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ETV6 (ETS Variant Transcription Factor 6) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

BRAF V600E • BRAF V600 • FGFR2 mutation • FGFR2 fusion • HRAS mutation • AKT1 mutation

Real-world effectiveness of molecular-matched therapies in salivary gland cancer. (PubMed, ESMO Open)

Comprehensive molecular testing in SGC may allow access to MMT, with a subset of patients experiencing clinical benefit from this strategy.

1 month ago

Journal • Real-world evidence • Tumor mutational burden • PD(L)-1 Biomarker

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ETV6 (ETS Variant Transcription Factor 6)

BRAF V600E • TMB-H • BRAF V600 • RAS wild-type • HRAS mutation

Opdivo (nivolumab) • Yervoy (ipilimumab) • Zelboraf (vemurafenib) • Vitrakvi (larotrectinib) • Cotellic (cobimetinib)

2ms

Association between 8-OHdG Levels and Eosinophil Counts in Chronic Rhinosinusitis with Nasal Polyps. (PubMed, Int Arch Otorhinolaryngol)

Based on the results in the present cohort, higher levels of 8-OHdG, indicative of oxidative stress, are associated with higher eosinophil counts in CRSwNP. Additionally, HRAS and NRAS mutations do not occur in nasal polyps or occur at a very low frequency.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

KRAS mutation • NRAS mutation • RAS mutation • HRAS mutation

2ms

Impact of Copy-number Alterations on Human Papillomavirus (HPV)-Induced and HPV-Independent Penile Cancers. (PubMed, Lab Invest)

Together with mutations in PIK3CA, HRAS and FGFR3 they represent an alternative RTK/Ras/PI3K-mediated carcinogenesis pathway. More than half of advanced SCC irrespective of etiology harbored targetable CNA such as EGFR, MTAP, ATM.

2 months ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NRG1 (Neuregulin 1) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SOX2 • RAD21 (RAD21 Cohesin Complex Component) • WRN (WRN RecQ Like Helicase) • TP63 (Tumor protein 63) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • FANCD2 (FA Complementation Group D2) • BCL9L (BCL9 Like)

KRAS mutation • PIK3CA mutation • EGFR amplification • TP53 wild-type • HRAS mutation

2ms

MegaMOST: A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (clinicaltrials.gov)

P2, N=455, Recruiting, Centre Leon Berard | Trial completion date: Nov 2026 --> Oct 2027 | Trial primary completion date: Feb 2026 --> Oct 2026

2 months ago

Trial completion date • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • FLT1 (Fms-related tyrosine kinase 1) • CDK6 (Cyclin-dependent kinase 6) • CCND3 (Cyclin D3) • TYRO3 (TYRO3 Protein Tyrosine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF mutation • NRAS mutation • BRAF V600 • KIT mutation • CDKN2A deletion • HRAS mutation • KRAS G12 • PDGFRA mutation • KRAS amplification • NRAS G12

Mekinist (trametinib) • Tafinlar (dabrafenib) • Alecensa (alectinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Kisqali (ribociclib) • Ayvakit (avapritinib) • siremadlin (HDM201)