News - NRAS G12 - LARVOL VERI

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer (clinicaltrials.gov)

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

1 day ago

Trial completion date

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

KRAS mutation • NRAS mutation • BRAF V600 • BRAF wild-type • RAS wild-type • HRAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS Q61

Mekinist (trametinib) • omipalisib (GSK2126458)

Cutaneous Epithelioid/Pleomorphic Rhabdomyosarcoma, Melanoma in Disguise? An Immunohistochemical, Molecular and Epigenetic Study of 13 Patients. (PubMed, Mod Pathol)

The majority of cutaneous epithelioid/pleomorphic rhabdomyosarcoma show clinical, genetic, and epigenetic profiles similar to melanoma, suggesting that a major subset represents transdifferentiated melanoma.

3 days ago

Journal • Tumor mutational burden

BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TFCP2 (Transcription Factor CP2)

BRAF V600E • NRAS Q61 • NRAS G12

Retrospective Comparison of Operational Metrics Across Diagnostic Approaches for Molecular Testing in Lung and Colon Cancers in a Community-Based Setting. (PubMed, Arch Pathol Lab Med)

OFA balances TAT, QNS, and detection, whereas SO-NGS offers comprehensive detection with longer TAT and higher QNS. An optimized assay combining SGP's speed, OFA's reliability, and SO-NGS's comprehensiveness could improve outcomes.

8 days ago

Retrospective data • Journal

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) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • 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) • TYK2 (Tyrosine Kinase 2) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS G12C • HER-2 amplification • HER-2 mutation • MET exon 14 mutation • KRAS G12 • KRAS amplification • NRAS G12

Oncomine Focus Assay

15d

The polyamine inhibitor SAM486A increases the efficacy of adagrasib in non-small cell lung cancer cells harboring KRASG12C mutation. (PubMed, Biol Res)

Our results suggest that targeting polyamine metabolism with SAM486A enhances the efficacy of KRASG12C inhibitors and may mitigate resistance. This combination represents a promising therapeutic approach for KRASG12C-mutant NSCLC and warrants further clinical investigation.

15 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PCNA (Proliferating cell nuclear antigen)

KRAS mutation • KRAS G12C • KRAS wild-type • RAS wild-type • KRAS G12 • NRAS Q61 • NRAS G12

Krazati (adagrasib)

17d

Structure-Guided Development of NRAS G12D Inhibitors Based on a 5‑Azaindole Core. (PubMed, ACS Med Chem Lett)

The development process revealed key insights into gaining selectivity between NRAS and KRAS proteins. Notably, stabilization of the p-loop and substitution toward Leu 95 while maintaining key interactions with Asp12, Gly60, and Asp69 improved NRAS G12D potency and resulted in selectivity against wild-type KRAS/non-responder.

17 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)

NRAS mutation • KRAS G12D • KRAS wild-type • RAS wild-type • KRAS G12 • NRAS G12

26d

Revealing conformational changes of GTP-bound NRAS mutants probed by GaMD and Markov state models. (PubMed, Phys Chem Chem Phys)

Furthermore, mutations induce specific changes in the protein's internal communication networks. These insights into the dynamic properties of oncogenic NRAS mutants provide a robust mechanistic foundation for understanding aberrant signaling and guiding the rational design of novel anti-cancer therapeutics.

26 days ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog)

NRAS mutation • RAS wild-type • NRAS Q61 • NRAS wild-type • NRAS G12

Case Report: A rare case of synchronous ovarian mixed germ cell tumor and mast cell leukemia in a pediatric patient. (PubMed, Front Oncol)

Targeted therapy with avapritinib and ruxolitinib was initiated but yielded limited response. Given the consistent co-occurrence of KIT mutations in previously reported similar cases, we propose the recognition of a distinct disease entity: ovarian germ cell tumor/mastocytosis with KIT mutations. This report emphasizes the importance of early genetic profiling and multidisciplinary collaboration in diagnosing and managing rare, genetically unified malignancies in pediatric oncology.

1 month ago

Journal

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • AFP (Alpha-fetoprotein)

TP53 mutation • NRAS mutation • KIT mutation • AFP elevation • NRAS G12 • TP53 Y220C

Jakafi (ruxolitinib) • Ayvakit (avapritinib)

2ms

IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma (clinicaltrials.gov)

P1, N=51, Completed, InxMed (Shanghai) Co., Ltd. | Active, not recruiting --> Completed | N=120 --> 51

2 months ago

Trial completion • Enrollment change

NRAS (Neuroblastoma RAS viral oncogene homolog)

NRAS mutation • NRAS Q61 • NRAS G12 • NRAS G13

Tecentriq (atezolizumab) • Cotellic (cobimetinib) • ifebemtinib (IN10018)

2ms

SOX2 confers tumour permissiveness in a specific skin progenitor population. (PubMed, Nat Commun)

However, SOX2 is uniquely upregulated in progenitor-derived tumours and is expressed in 20% of human cSCC, indicating it might mark tumours arising from committed progenitors. Here, we show that SOX2 overexpression, along with MAPK activation, in progenitors induces a stem-like state and renders this otherwise resistant population permissive to rapid transformation.

2 months ago

Journal

SOX2

BRAF V600E • BRAF V600 • NRAS G12

2ms

Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer (clinicaltrials.gov)

P1/2, N=30, Recruiting, Changhai Hospital | Trial completion date: Mar 2025 --> Dec 2028 | Trial primary completion date: Dec 2024 --> Jun 2027

2 months ago

Trial completion date • Trial primary completion date • 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 • NRAS G12

cyclophosphamide • fludarabine IV

3ms

Widespread Epistasis between Cancer Driver Mutations and Allele-Specific Copy Number Variations. (PubMed, bioRxiv)

Lung cancer patients carrying co-occurrences of somatic mutation-CNVs in TP53 and KRAS showed poorer survival than those carrying the same gene mutations. These findings reveal epistasis of cancer mutations and CNVs at an allelic resolution, suggesting specific genomic events to enhance patient stratification and therapeutic targeting.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

TP53 mutation • BRAF V600E • KRAS mutation • KRAS G12C • BRAF V600 • KRAS G12 • NRAS Q61 • AKT1 mutation • NRAS G12 • IDH1 R132

3ms

Translational Relevance of the Genomic Landscape of KRASG12D-Mutant Colorectal and Pancreatic Cancers. (PubMed, Target Oncol)

We described the genomic landscape of KRASG12D-mutant CRC and PDAC, demonstrating that cases often have additional oncogenic alterations linked to resistance to KRAS inhibition. These alterations are also associated with a worse prognosis. Recognizing these alterations may inform new therapeutic strategies. Further studies are warranted to validate these findings in ongoing clinical trials.

3 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog)

KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • KRAS G12D • EGFR amplification • KRAS G12 • KRAS amplification • NRAS G12