News - HRAS mutation - LARVOL VERI

Mutant RAS-driven secretome causes skeletal muscle defects in breast cancer. (PubMed, Cancer Res Commun)

Circulating levels of the chemokine CXCL1 were elevated only in animals with tumors containing HRASG12V mutation. Since RAS pathway aberrations are found in 19% of cancers, evaluating skeletal muscle defects in the context of genomic aberrations in cancers, particularly RAS pathway mutations, may accelerate development of therapeutic modalities to overcome cancer-induced systemic effects.

3 days ago

Journal • BRCA Biomarker

ER (Estrogen receptor) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • RAS (Rat Sarcoma Virus) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • MIR486-1 (MicroRNA 486-1) • PAX7 (Paired Box 7)

BRCA2 mutation • ER positive • PIK3CA mutation • PIK3CA H1047R • RAS mutation • HRAS mutation • PGR positive • NRAS G12 • HRAS G12V

Genomic and Transcriptomic Landscape of RET Wild-Type Medullary Thyroid Cancer and Potential Use of Mitogen-Activated Protein Kinase-Targeted Therapy. (PubMed, J Am Coll Surg)

We identified molecular alterations and immune-related features that distinguish wtRET from mutRET MTC. While RET mutation drives MTC in the absence of other alterations, we showed that wtRET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with oncology immune-oncology agents for selected patients with wtRET MTC.

3 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • STK11 (Serine/threonine kinase 11) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1)

PD-L1 expression • KRAS mutation • TMB-H • BRAF mutation • STK11 mutation • NF1 mutation • RET mutation • VHL mutation • HRAS mutation • RET wild-type

Retevmo (selpercatinib)

17d

Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. (PubMed, Nature)

Here we describe RMC-7977, a reversible, tri-complex RAS inhibitor with broad-spectrum activity for the active state of both mutant and wild-type KRAS, NRAS and HRAS variants (a RAS(ON) multi-selective inhibitor). Thus, RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRAS-mutant solid tumours (ClinicalTrials.gov identifier: NCT05379985).

17 days ago

Journal

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

KRAS mutation • NRAS mutation • KRAS wild-type • RAS wild-type • HRAS mutation • NRAS wild-type • HRAS G12C • HRAS wild-type

RMC-6236 • RMC-7977

18d

Probing RAS Function Using Monobody and NanoBiT Technologies. (PubMed, Methods Mol Biol)

To do this, we have exploited the use of monobody (Mb) technology to develop specific protein-based inhibitors of selected RAS isoforms and mutants (Spencer-Smith et al., Nat Chem Biol 13:62-68, 2017; Khan et al., Cell Rep 38:110322, 2022; Wallon et al., Proc Natl Acad Sci USA 119:e2204481119, 2022; Khan et al., Small GTPases 13:114-127, 2021; Khan et al., Oncogene 38:2984-2993, 2019). Herein, we describe our combined use of Mbs and NanoLuc Binary Technology (NanoBiT) to analyze RAS protein-protein interactions and to screen for RAS-binding small molecules in live-cell, high-throughput assays.

18 days ago

Journal

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

KRAS mutation • KRAS G12C • KRAS G12D • RAS mutation • HRAS mutation • HRAS G12C

24d

Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line. (PubMed, Hum Cell)

The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

24 days ago

Preclinical • Journal • MSi-H Biomarker

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • HRAS (Harvey rat sarcoma viral oncogene homolog) • FGFR (Fibroblast Growth Factor Receptor) • AXL (AXL Receptor Tyrosine Kinase) • ROR2 (Receptor Tyrosine Kinase Like Orphan Receptor 2)

TP53 mutation • MSI-H/dMMR • HRAS mutation

cisplatin • carboplatin

28d

Tipifarnib in Advanced Squamous NSCLC With Oncogen HRAS MutAtionS (clinicaltrials.gov)

P2, N=9, Terminated, Spanish Lung Cancer Group | Active, not recruiting --> Terminated; The recruitment was closed prematurely to due to slow recruitment.

28 days ago

Trial termination • Metastases

HRAS (Harvey rat sarcoma viral oncogene homolog)

HRAS mutation

Zarnestra (tipifarnib)

30d

Different oncogenes and reproductive histories shape the progression of distinct premalignant clones in multistage mouse breast cancer models. (PubMed, Am J Pathol)

However, parity decreased the overall prevalence of tumors bearing Krasmut, and the magnitude of this decrease depended on both the number and timing of pregnancies. These multistage models may be useful for elucidating biological features of premalignant mammary neoplasia.

30 days ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RAS (Rat Sarcoma Virus)

KRAS mutation • NRAS mutation • PIK3CA H1047R • RAS mutation • HRAS mutation • NRAS Q61 • MYC expression • NRAS Q61L • KRAS Q61L

BRAF Mutated and Morphologically Spitzoid Tumors, a Subgroup of Melanocytic Neoplasms Difficult to Distinguish From True Spitz Neoplasms. (PubMed, Am J Surg Pathol)

Expert melanoma pathologists in this study favored a diagnosis of ST in nearly half of the BAMS cases. There are BAMS cases that even experts cannot morphologically distinguish from true Spitz neoplasms.

1 month ago

Journal

BRAF (B-raf proto-oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog)

BRAF mutation • HRAS mutation

A Genomic Urine Assay for Surveillance of Patients with Bladder Cancer Treated with Radiotherapy. (PubMed, Eur Urol Open Sci)

However, interpretation of cystoscopy is difficult due to the effects of radiation on the bladder lining. Hence, we analyzed the diagnostic value of a molecular urine test to detect recurrent disease in bladder cancer patients treated by radiotherapy, and we showed that the urine test has the potential to limit the number of cystoscopies.

1 month ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • TWIST1 (Twist Family BHLH Transcription Factor 1) • ONECUT2 (One Cut Homeobox 2)

HRAS mutation

Characterization of Ras Y4H mutants in Drosophila. (PubMed, MicroPubl Biol)

In humans, rare histidine substitution mutations at Y4 are found in HRas in cerebellar glioblastomas (cGBMs). We report here that analogous Y4H mutations in Drosophila Ras make it less sensitive to Rabex-5-mediated ubiquitination in cells and show increased frequency of vein phenotypes per wing compared to wild-type Ras, which would be consistent with Ras gain-of-function and with their appearance in human cGBMs.

1 month ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog) • RAS (Rat Sarcoma Virus)

RAS mutation • RAS wild-type • HRAS mutation

Farnesyltransferase inhibitors have antitumoral effects in mutant KRAS containing cancer cells in preclinical models (PubMed, Magy Onkol)

Accordingly, we have tested FTIs (tipifarnib and lonafarnib) in G12C mutant human cancer cell lines in vitro and in vivo. At last, we have also tested FTIs on G12V mutant human cancer cells and again we have detected antitumoral effects. We suggest that FTIs may have clinical relevance outside the HRAS mutant cancers.

1 month ago

Preclinical • Journal

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

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • HRAS mutation • HRAS G12C

Zarnestra (tipifarnib)

Testing the Combination of the Anticancer Drugs ZEN003694 and Binimetinib in Patients With Advanced/Metastatic or Unresectable Solid Tumors With RAS Alterations and Triple Negative Breast Cancer (clinicaltrials.gov)

P1, N=42, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

1 month ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PGR (Progesterone receptor) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1)

BRAF mutation • HER-2 amplification • NF1 mutation • HRAS mutation • BRAF fusion

Mektovi (binimetinib) • ZEN-3694

2ms

Genetic landscape of 482 thyroid carcinomas: analysis with the national datacenter for cancer genomic medicine in Japan. (PubMed, Endocrine)

PTC was the most common histologic type of TC for which genetic profiling was performed in Japan, followed by ATC. Since the most common targetable mutation is the BRAF mutation, practical application of BRAF-targeted therapy can be an important treatment option for Japanese patients with TC.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase)

BRAF V600E • KRAS mutation • BRAF V600 • RET mutation • HRAS mutation • TERT mutation • TERT promoter mutation

FoundationOne® CDx

2ms

RAS-Mutated Cytologically Indeterminate Thyroid Nodules: Prevalence of Malignancy and Behavior Under Active Surveillance. (PubMed, Thyroid)

We describe the behavior of RAS-mutant ITNs under AS and find that most demonstrate stability over time. Of the resected RAS-mutant nodules, most were benign; of the cancers, most were ATA low-risk. Immediate surgical resection of all RAS-mutant ITNs appears to be a low-value practice. Further research is needed to help define cases most appropriate for AS or immediate surgery.

2 months ago

Journal

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

KRAS mutation • NRAS mutation • RAS mutation • HRAS mutation

2ms

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 2024 --> Jan 2025

2 months ago

Trial completion date • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • EGF (Epidermal growth factor)

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 • HRAS Q61

Mekinist (trametinib)

2ms

Genomic Insights into Bone Sarcomas Originating from Infarcts (USCAP 2024)

Bone sarcomas associated with infarcts exhibit genomic instability, with pronounced copy number variations, especially in Chromosome 12. CDKN2A/B homozygous deletion is highly prevalent, whereas TP53 alterations appear less frequent than in osteosarcomas. MDM2 amplification and H3.3-G34 mutations are recurrent (33%).

2 months ago

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRD (Homologous Recombination Deficiency) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • MDM2 (E3 ubiquitin protein ligase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

PIK3CA mutation • HRD • MDM2 amplification • CDKN2A deletion • HRAS mutation • HRAS G13R • PIK3CA E542K • PIK3CA E542 • HRAS G13R

TruSight Oncology 500 Assay

3ms

The Molecular Landscape of Thymic Epithelial Tumors: A Comprehensive Review. (PubMed, Int J Mol Sci)

Targeted therapies, and ongoing clinical trials show promising results, addressing challenges rooted in the scarcity of actionable mutations and limited genomic understanding. International collaborations and data-sharing initiatives are crucial for breakthroughs in TETs research.

3 months ago

Review • Journal • Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog)

TP53 mutation • TMB-L • HRAS mutation

3ms

Conformational States of the GDP- and GTP-Bound HRAS Affected by A59E and K117R: An Exploration from Gaussian Accelerated Molecular Dynamics. (PubMed, Molecules)

Since the switch domains are crucial for the binding of HRAS to effectors, any alterations in their interactions or conformational states will undoubtedly disrupt the activity of HRAS. This research provides valuable information for the design of drugs targeting HRAS.

3 months ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog)

HRAS mutation

3ms

RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains. (PubMed, J Cell Biol)

Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, to the PM and differentially facilitates the recognition of PS acyl chains...Distribution of these KRAS4B oncogenic mutants favors different nanoscale membrane topography. Thus, RAS G-domains allosterically facilitate membrane lateral distribution.

3 months ago

Journal

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

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G13D • RAS mutation • HRAS mutation • KRAS G12 • HRAS G12C

3ms

The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms. (PubMed, Endocr Pathol)

However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.

3 months ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • RAS (Rat Sarcoma Virus)

HRAS mutation • TERT mutation • TERT promoter mutation

3ms

Evolutionary dynamics of tipifarnib in HRAS mutated head and neck squamous cell carcinoma. (PubMed, Oral Oncol)

Lastly, in HRAS-mutated PDXs and in the syngeneic HRAS model, we demonstrated that tipifarnib efficacy is limited by activation of the AKT pathway, and dual treatment with tipifarnib and the PI3K inhibitor, BYL719, resulted in enhanced anti-tumor efficacy. Our case study highlights the potential of targeting HRAS mutations with tipifarnib in R/M HNSCC and identifies potential mechanisms of acquired resistance to tipifarnib, along with immuno-, chemo-, and radiation therapy. Preclinical results provide a firm foundation for further investigation of drug combinations of HRAS-and PI3K -targeting therapeutics in R/M HRAS-driven HNSCC.

3 months ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog) • AXL (AXL Receptor Tyrosine Kinase) • YAP1 (Yes associated protein 1)

HRAS mutation • NRAS G12 • HRAS G12S

Piqray (alpelisib) • Zarnestra (tipifarnib)

4ms

The Diagnostic Utility of Repeat Fine-needle Aspirations of Benign Thyroid Nodules. (PubMed, Eur Thyroid J)

The total cost for workup of previously benign nodules was $285,454. Conclusions Repeat FNA biopsies did not provide an additional diagnostic value in the evaluation of benign thyroid nodules, and often led to unwarranted follow-up procedures and significantly increased health care cost.

4 months ago

Journal

RET (Ret Proto-Oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase)

RET fusion • HRAS mutation • TERT mutation • TERT promoter mutation

4ms

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients (clinicaltrials.gov)

P1/2, N=8, Suspended, National Cancer Institute (NCI) | N=110 --> 8 | Recruiting --> Suspended

4 months ago

Enrollment change • Trial suspension • IO biomarker

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

KRAS mutation • NRAS mutation • KRAS G12V • HRAS mutation • KRAS G12 • NRAS G12 • HLA-A*11 • NRAS G12V

cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)

4ms

FIT-001: KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (clinicaltrials.gov)

P1, N=270, Recruiting, Kura Oncology, Inc.

4 months ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

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

KRAS mutation • HRAS mutation • HRAS overexpression

Cabometyx (cabozantinib tablet) • KO-2806

4ms

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

P2, N=425, Recruiting, Centre Leon Berard

4 months ago

Trial completion date • Trial primary completion date • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • 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) • 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)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • CDKN2A deletion • HRAS mutation • PTPN11 mutation • CCND1 amplification • KRAS amplification • BRAF amplification

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

4ms

A Phase 1/2a Study of IMM-1-104 in Participants With Previously Treated, RAS-Mutant, Advanced or Metastatic Solid Tumors (clinicaltrials.gov)

P1/2, N=210, Recruiting, Immuneering Corporation | N=156 --> 210

4 months ago

Enrollment change • Metastases

KRAS (KRAS proto-oncogene GTPase) • HRAS (Harvey rat sarcoma viral oncogene homolog) • APC (APC Regulator Of WNT Signaling Pathway)

KRAS mutation • NRAS mutation • KRAS wild-type • RAS mutation • HRAS mutation • APC mutation

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • IMM-1-104

4ms

Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy. (PubMed, Cancer Res Treat)

According to our comprehensive analysis, HG non-invasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Non-invasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

4 months ago

Journal

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

FGFR3 mutation • HRAS mutation

4ms

RAS Family Gene Mutations, Clinicopathological Features, and Spread Patterns of Inverted Urothelial Papilloma of the Bladder. (PubMed, Am J Surg Pathol)

No recurrence or carcinoma development was observed in any of the IUP cases during the follow-up period. Thus, we confirmed the importance of RAS pathway activation in IUP pathogenesis, an association between RAS family gene mutations and IUP subtypes, and the spread patterns of IUP cells within the surface.

4 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RAS (Rat Sarcoma Virus)

TP53 mutation • KRAS mutation • NRAS mutation • RAS mutation • HRAS mutation • NRAS Q61 • NRAS Q61R • HRAS Q61R

4ms

Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman's Conundrum. (PubMed, Cancers (Basel))

A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients.

4 months ago

Retrospective data • Review • Journal

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • 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) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)

BRAF mutation • NTRK1 fusion • NTRK2 fusion • ALK fusion • CDKN2A deletion • HRAS mutation • TERT mutation

4ms

Schimmelpenning-Feuerstein-Mims syndrome with orbital choristoma and KRAS mutation: a current review and novel case report. (PubMed, Ophthalmic Genet)

This is the first case description of a KRAS mutation identified in an orbital choristoma in SFMS. The disease is described under various names in the literature, and we propose that all syndromic cases with mosaic RAS mutations be reported under the eponym, SFMS.

4 months ago

Review • Journal

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

KRAS mutation • NRAS mutation • KRAS G12D • RAS mutation • HRAS mutation • KRAS G12 • NRAS G12D

4ms

Performance of the OncoUrine test on predicting patients who can avoid Re-TURBT and prognosis: A prospective, multicenter clinical study. (ASCO-GU 2024)

OncoUrine test after initial TURBT for NMIBC showed promise as to guide patient selection for Re-TURBT and risk stratification in the management of NMIBC. Clinical trial information: NCT05112523.

4 months ago

Clinical

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TERT (Telomerase Reverse Transcriptase) • ERCC2 (Excision repair cross-complementation group 2) • KDM6A (Lysine Demethylase 6A) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ONECUT2 (One Cut Homeobox 2)

TP53 mutation • KRAS mutation • PIK3CA mutation • HER-2 mutation • HRAS mutation • U2AF1 mutation • ERBB3 mutation • TERT mutation

5ms

Palbociclib and Binimetinib in RAS-Mutant Cancers, A ComboMATCH Treatment Trial (clinicaltrials.gov)

P2, N=199, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

5 months ago

Enrollment open

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

BRAF V600E • KRAS mutation • KRAS G12C • HRAS mutation • KRAS G12 • HRAS G12C

Ibrance (palbociclib) • Mektovi (binimetinib)

5ms

Calcaneus metastasis: a rare presentation of poorly differentiated thyroid cancer. (PubMed, Endocrinol Diabetes Metab Case Rep)

PAX-8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas. The importance of searching for gene mutations to decide the treatment of PDTC.

5 months ago

Journal • Tumor mutational burden • IO biomarker

TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog) • GNA13 (G Protein Subunit Alpha 13) • NKX2-1 (NK2 Homeobox 1) • PAX8 (Paired box 8)

TMB-H • HRAS mutation

5ms

Comprehensive analysis of miRNA-mRNA regulatory pairs associated with colorectal cancer and the role in tumor immunity. (PubMed, BMC Genomics)

We found that 2 miRNAs by targeting 2 metastasis-related mRNAs were correlated with tumor-infiltrating macrophages, HRAS, and BRAF gene mutation status. Our results established the diagnostic model containing 2 miRNAs and their respective targeted mRNAs to distinguish CRCs and normal controls and displayed their complex roles in CRC pathogenesis especially tumor immunity.

5 months ago

Journal • Tumor mutational burden

BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog) • MIR139 (MicroRNA 139) • MIR20A (MicroRNA 20a) • STC1 (Stanniocalcin 1)

BRAF mutation • HRAS mutation

5ms

Characteristic Mutational Damages in Gastric and Colorectal Adenocarcinomas. (PubMed, Asian Pac J Cancer Prev)

By identifying specific gene mutations and differences in genetic markers, the study provided insights for the development of targeted diagnostic methods and personalised treatment strategies, ultimately improving the clinical outcomes in the field of oncology.

5 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

TP53 mutation • KRAS mutation • NRAS mutation • TP53 deletion • HRAS mutation

5ms

Spitz tumor with RAF1 fusion: A report of 3 cases. (PubMed, Ann Diagn Pathol)

Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.

5 months ago

Journal

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • 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) • HRAS (Harvey rat sarcoma viral oncogene homolog) • BAP1 (BRCA1 Associated Protein 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)

BRAF mutation • NTRK1 fusion • NTRK2 fusion • ALK fusion • HRAS mutation

5ms

Whole exome sequencing uncovers HRAS mutations as potential mediators of resistance to metronomic chemotherapy. (PubMed, Gene)

Our findings corroborate the molecular heterogeneity of recurrent HNSCC tumors and establish an association between HRAS mutations and resistance to metronomic chemotherapy, suggesting HRAS as a potential therapeutic target. Combining HRAS inhibitors with metronomic regimens could improve treatment sensitivity in HRAS-mutated HNSCC patients. Further studies are needed to fully elucidate the genomic mechanisms underlying the response to metronomic chemotherapy.

5 months ago

Journal

TP53 (Tumor protein P53) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • FAT1 (FAT atypical cadherin 1) • CASP8 (Caspase 8) • KMT2B (Lysine Methyltransferase 2B)

HRAS mutation

5ms

Clinical, Morphologic, and Molecular Features of Benign and Intermediate-grade Melanocytic Tumors With Activating Mutations in MAP2K1. (PubMed, Am J Surg Pathol)

A significant proportion of melanomas also have activating MAP2K1 mutations. In-frame deletions are predominantly seen in the benign and intermediate-grade cases, and missense mutations are predominantly seen in melanomas.

5 months ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

HRAS mutation

5ms

The Spectrum of HPV-independent Penile Intraepithelial Neoplasia: A Proposal for Subclassification. (PubMed, Am J Surg Pathol)

Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS.

5 months ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

TP53 mutation • PIK3CA mutation • TP53 wild-type • CDKN2A mutation • HRAS mutation • CDKN2A negative • CDKN2A overexpression • TP53 overexpression

5ms

Phytocompounds from essential oil of Mentha aquatica L. cv. Lime prevent vemurafenib-promoted skin carcinogenesis via inhibiting HRAS keratinocytes and reprogramming macrophage activities. (PubMed, Phytomedicine)

This study demonstrates that EO and L + C in combination prevent PLX4032-induced cutaneous side-effects and skin carcinogenesis in mice through reprogramming the macrophage cell population and inhibiting keratinocyte activity. Both mint EO and the natural products L + C can be considered to be effective chemopreventive agents that might be useful in reducing cutaneous lesions in human patients administrated with BRAF inhibitors.

5 months ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog) • CD163 (CD163 Molecule)

HRAS mutation

Zelboraf (vemurafenib)

6ms

TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas. (PubMed, Head Neck)

The study suggests that OCSCC with pTERT mutation represents a distinct subgroup with unique clinical and genetic characteristics.

6 months ago

Journal

TP53 (Tumor protein P53) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CASP8 (Caspase 8)

TP53 mutation • HRAS mutation • TERT mutation • TERT promoter mutation

6ms

DEVELOPMENT OF A GENOMIC PREDICTION MODEL FOR UPPER TRACT UROTHELIAL CARCINOMA STAGE (SUO 2023)

We developed a three-gene model that was predictive of high stage disease. Our model significantly outperforms the accuracy of uretereoscopic biopsy in a development set but is yet to be validated in this population. Ultimately, the clinical utility of this model may be seen not only in improving ureteroscopic biopsy accuracy, but also as applied to sequenced urinary tumor DNA as a non-invasive biomarker.

6 months ago

TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog)

HRAS mutation

MSK-IMPACT