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NRAS (Neuroblastoma RAS viral oncogene homolog)

News alerts, weekly reports and conference planners

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

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

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 (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) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

EGFR exon 20 insertion • EGFR exon 20 mutation

Oncomine™ Pan-Cancer Cell-Free Assay

High Analytical Sensitivity and Specificity of the AVENIO Tumor Tissue CGP Automated Assay for Detecting Genomic Alterations in FFPE Tumor Tissue (AMP 2024)

The AVENIO CGP assay is an end-to-end platform for tumor genomic profiling, with proven high analytical sensitivity and specificity. Its superb performance makes it well suited for translational research, providing deep genomic analyses to accelerate cancer research.

2 days ago

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog)

HER-2 amplification • ALK fusion • NRAS G13

AVENIO Tumor Tissue CGP Kit • PGDx elio™ tissue complete assay

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®

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

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 genomic landscape of papillary thyroid carcinoma on next-generation sequencing in patients undergoing total thyroidectomy. (PubMed, World J Surg)

This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases.

9 days ago

Journal • Next-generation sequencing

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • CDH1 (Cadherin 1)

BRAF mutation • PIK3CA mutation • ALK mutation • PTCH1 mutation

Fasting-mimicking diet potentiates anti-tumor effects of CDK4/6 inhibitors against breast cancer by suppressing NRAS- and IGF1-mediated mTORC1 signaling. (PubMed, Drug Resist Updat)

Our data demonstrate that FMD overcomes resistance and potentiates the anti-tumor effect of CDK4/6i by inhibiting mTORC1 signaling via lowering the levels of IGF1 and RAS, providing the rationale for clinical investigation of a potential FMD-CDK4/6i strategy in breast cancer.

9 days ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • IGF1 (Insulin-like growth factor 1)

Verzenio (abemaciclib)

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

Mitochondrial Proteome Defined Molecular Pathological Characteristics of Oncocytic Thyroid Tumors. (PubMed, Endocr Pathol)

Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management.

10 days ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked)

NRAS mutation • HRAS mutation • TERT mutation • TERT promoter mutation

11d

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Single-Center Experience. Clinical Characterization, Mutational Landscape, and Clinical Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation Intensive Therapy. (PubMed, Actas Dermosifiliogr)

This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

11 days ago

Clinical data • Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • CLEC4C (C-Type Lectin Domain Family 4 Member C)

12d

Association between KRAS mutation and alcohol consumption in Brazilian patients with colorectal cancer. (PubMed, Sci Rep)

Our findings support a relationship between alcohol consumption and the rs121913529 mutation, which is classified as pathogenic for colorectal cancer. Thus, further studies investigating the link between alcohol consumption, colorectal carcinogenesis and tumor progression ought to be conducted.

12 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)

TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation

12d

Recapitulating the adenoma-carcinoma sequence by selection of four spontaneous oncogenic mutations in mismatch-repair-deficient human colon organoids. (PubMed, Nat Cancer)

Here, we demonstrate that long-term culture of mismatch-repair-deficient organoids allows the selection of spontaneous oncogenic mutations through the sequential withdrawal of Wnt agonists, epidermal growth factor (EGF) agonists and the bone morphogenetic protein (BMP) antagonist Noggin, while TP53 mutations were selected through the addition of Nutlin-3...Quadruple-pathway (Wnt, EGF receptor, p53 and BMP) mutant organoids formed solid tumors upon xenotransplantation. This demonstrates that carcinogenesis can be recapitulated in a DNA repair-mutant background through in vitro selection that targets four consecutive cancer pathways.

12 days ago

Journal • Mismatch repair

NRAS (Neuroblastoma RAS viral oncogene homolog) • ACVR2A (Activin A Receptor Type 2A)

TP53 mutation • MSI-H/dMMR

Nutlin-3

14d

Non-small cell lung carcinoma with co-expression of TTF1 and p40: a clinicopathological analysis of six cases (PubMed, Zhonghua Bing Li Xue Za Zhi)

NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.

14 days ago

Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • EML4 (EMAP Like 4) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1)

EGFR mutation • NRAS mutation • PIK3CA mutation • ALK mutation • NKX2-1 expression • TTF1 expression

14d

Extracellular vesicles powered cancer immunotherapy: Targeted delivery of adenovirus-based cancer vaccine in humanized melanoma model. (PubMed, J Control Release)

This study explores the potential of EVs for the selective delivery of cancer vaccines against malignancies, such as NRAS melanoma. Overall, this research could pave the way for applying autologous EVs as a safe and efficacious tool for targeted cancer therapy.

14 days ago

Journal • IO biomarker

NRAS (Neuroblastoma RAS viral oncogene homolog) • CD40LG (CD40 ligand)

NRAS mutation

15d

Selective Clonal Regression After Interferon Therapy in Metastatic Melanoma. (PubMed, Am J Dermatopathol)

We present an example of the latter, where therapy with interferon induced regression of the metastatic-capable melanocytic population, with only the primary tumor melanocytic population persisting. To confirm this, we demonstrated BRAF mutational similarity between the 2 populations, and an additional NRAS mutation in the metastatic population, which was absent in the primary tumor.

15 days ago

Journal • Metastases

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

BRAF mutation • NRAS mutation

15d

Pharmacologic restoration of GTP hydrolysis by mutant RAS. (PubMed, Nature)

RAS mutants most sensitive to stimulation of GTPase activity were more susceptible to treatment compared to mutants whose hydrolysis could not be enhanced, suggesting that pharmacologic stimulation of hydrolysis potentiates the therapeutic effects of tri-complex inhibitors for specific RAS mutants. This study lays the foundation for developing a new class of therapeutics that inhibit cancer growth by stimulating mutant GTPase activity.

15 days 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 • RAS mutation • HRAS mutation

16d

CDK4 gene copy number increase and concurrent genetic changes in acral melanoma of a Chinese cohort. (PubMed, Pathology)

CDK4 high-level copy number increase coexists with other pathogenic mutations in AM. CDK4 appears to be a promising target for AM treatment and is expected to be combined with other targeted therapies.

16 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • BCL2L11 (BCL2 Like 11)

BRAF mutation • NRAS mutation • HER-2 mutation • BCL2L1 mutation • CDK4 mutation

17d

BRAF and NRAS Mutations and the Association with Prognosis of Acral Lentiginous and Nodular Melanomas in Indonesia. (PubMed, Asian Pac J Cancer Prev)

In this study, melanoma patients are largely diagnosed at the late stages with ulceration and involvement of regional lymph nodes. BRAF mutations are associated with lower survival of cutaneous melanoma patients.

17 days ago

Journal

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

BRAF mutation • NRAS mutation • NRAS mutation + BRAF mutation

18d

Prognostic impact of next-generation sequencing on myelodysplastic syndrome: A single-center experience. (PubMed, Medicine (Baltimore))

According to early findings, NGS panels are extremely effective instruments that provide an entirely new viewpoint on the disease for particular individuals. Future prognostications will depend more on NGS because those who exhibit normal cytogenetics may additionally have gene mutations.

18 days ago

Journal • Next-generation sequencing

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • 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) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6)

ASXL1 mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • PHF6 mutation

18d

Association of mutation profiles with metastasis in patients with non-small cell lung cancer. (PubMed, Front Oncol)

Patients with ALK mutant, BRAF mutant or NRAS mutant were more prone to metastasis, while the HER 2 mutation group was less metastatic. Patients with EGFR mutant NSCLC are more likely to develop bone, lung, or brain metastasis.

18 days ago

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) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • ALK mutation • MET mutation • EGFR mutation + PIK3CA mutation

18d

Mirdametinib + BGB-3245 in Advanced Solid Tumors (clinicaltrials.gov)

P1/2, N=23, Active, not recruiting, SpringWorks Therapeutics, Inc. | Recruiting --> Active, not recruiting | N=136 --> 23

18 days ago

Enrollment closed • Enrollment change • Combination therapy • Metastases

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

KRAS mutation • BRAF mutation • NRAS mutation • BRAF fusion

mirdametinib (PD-0325901) • brimarefenib (BGB-3245)

18d

Study of the Safety and Pharmacokinetics of BGB-283 (Lifirafenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors (clinicaltrials.gov)

P1, N=105, Recruiting, BeiGene | Phase classification: P1b --> P1

18 days ago

Phase classification

NRAS (Neuroblastoma RAS viral oncogene homolog)

NRAS mutation

mirdametinib (PD-0325901) • lifirafenib (BGB-283)

19d

Two Decades of Progress in Personalized Medicine of Colorectal Cancer in Serbia-Insights from the Institute for Oncology and Radiology of Serbia. (PubMed, Biomedicines)

Although significant improvements in CRC management have occurred globally in recent years, a strategic approach leading to population-based systemic solutions is required. The high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy will be especially important factors for countries with limited healthcare resources like Serbia.

19 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

KRAS mutation • BRAF mutation • NRAS mutation • BRAF V600 • RAS mutation • CHEK2 mutation

19d

An Analysis of Genetic Polymorphisms in 76 Genes Related to the Development of Ovarian Tumors of Different Aggressiveness. (PubMed, Int J Mol Sci)

Our results shed new light on the similarities and differences in the polymorphic patterns between ovarian tumors of diverse aggressiveness. Furthermore, the biomarkers identified herein are of potential use as predictors of the prognosis and/or response to therapy.

19 days ago

Journal • BRCA Biomarker • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • TSC2 (TSC complex subunit 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • FANCF (FA complementation group F) • FANCI (FA Complementation Group I) • FANCD2 (FA Complementation Group D2)

BRAF V600E • BRAF V600 • FANCF mutation

19d

The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations. (PubMed, Sci Rep)

To our knowledge, this is the first report of prominent pervasive oncogenic role of RAS mutations revealed by gene dependency data that is beyond the current understanding of the oncogenic role of RAS genes and their well-known involved tissue types. Our findings strongly support RAS mutations as primary oncogenic drivers beyond traditionally recognized cancer types and offer insights into their tissue-specific permissiveness.

19 days ago

Journal

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

RAS mutation

21d

Loss of CCL28 and CXCL17 Expression and Increase in CCR1 Expression May Be Related to Malignant Transformation of LGBLEL into Lymphoma. (PubMed, Curr Issues Mol Biol)

The chemokine signaling pathway plays a role in the malignant transformation of LGBLEL. The decreased expression of CCL28 and CXCL17, coupled with the increased expression of CCR1, may be linked to the progression of LGBLEL into lymphoma.

21 days ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • CCL2 (Chemokine (C-C motif) ligand 2) • ADRB2 (Adrenoceptor Beta 2) • CCL22 (C-C Motif Chemokine Ligand 22) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • CCR1 (C-C Motif Chemokine Receptor 1)

21d

Atypical Exon 2/3 Mutants G48C, Q43K, and E37K Present Oncogenic Phenotypes Distinct from Characterized NRAS Variants. (PubMed, Cells)

Further, G48C, Q43K, and E37K all have less negative ΔG values, indicating a weaker GDP-binding affinity compared to wild-type NRAS. Taken together, the results suggest that oncogenic readouts of NRAS mutants are codon- and mutation-specific, with potential repercussions on the aggressiveness, resistance, and therapeutic response.

21 days ago

Journal

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

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

22d

Anti-Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial. (PubMed, JAMA Oncol)

Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS. ClinicalTrials.gov Identifier: NCT03181100.

22 days ago

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

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1)

BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • RAS mutation • HRAS mutation

Avastin (bevacizumab) • Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Cotellic (cobimetinib)

22d

Dual Immune Checkpoint Inhibition in Patients With Aggressive Thyroid Carcinoma: A Phase 2 Nonrandomized Clinical Trial. (PubMed, JAMA Oncol)

To evaluate the efficacy of anti-programmed cell death 1 nivolumab and anti-cytotoxic lymphocyte-associated protein 4 ipilimumab in patients with aggressive thyroid carcinoma. However, the signal observed in ATC may merit further evaluation. ClinicalTrials.gov Identifier: NCT03246958.

22 days ago

Clinical • P2 data • Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

BRAF V600E

Opdivo (nivolumab) • Yervoy (ipilimumab)

24d

eIF4F controls ERK MAPK signaling in melanomas with BRAF and NRAS mutations. (PubMed, Proc Natl Acad Sci U S A)

Furthermore, our quantitative analyses reveal a high spare signaling capacity in the ERK pathway, suggesting that eIF4F-dependent feedback keeps the majority of ERK molecules inactive under normal conditions. Overall, our findings highlight the crucial role of eIF4F in regulating ERK signaling flux and suggest that pharmacological eIF4F inhibitors can disrupt the negative feedback control of MAPK activity in melanomas with BRAF and NRAS activating mutations.

24 days ago

Journal

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6) • EGR1 (Early Growth Response 1) • EIF4G1 (Eukaryotic translation initiation factor 4 gamma, 1)

BRAF mutation • NRAS mutation • RAS mutation • NRAS mutation + BRAF mutation

26d

Oncogenic mutations in the TP53 and PI-3 kinase/AKT pathway are independent predictors of survival for advanced thyroid cancer: Analysis from the Molecular Screening and Therapeutics (MoST) program. (PubMed, Surgery)

TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations correlated with overall survival independently of histotype in patients with advanced thyroid cancer. Comprehensive genomic profiling has potential to inform prognosis, as well as identifying treatment targets for patients with advanced thyroid cancer.

26 days ago

Journal • Metastases

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase)

TP53 mutation • BRAF V600E • BRAF V600 • TERT mutation • TERT promoter mutation

27d

Molecular profiling of Oral epithelial dysplasia and Oral Squamous cell carcinoma using Next Generation Sequencing. (PubMed, J Stomatol Oral Maxillofac Surg)

The results obtained in this study explain the diverse genetic mutations in various grades of oral squamous cell carcinoma. Identification of these mutations would help in providing better treatment, designing a proper treatment plan for the patients with OSCC and support minimal intervention medicine.

27 days ago

Journal • Next-generation sequencing

NRAS (Neuroblastoma RAS viral oncogene homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

TP53 mutation • NRAS Q61 • CTNNB1 mutation • PDGFRA mutation • NRAS G13 • TP53 R248Q • TP53 R213

27d

Circulating tumor DNA in conjunctival melanoma: landscape and surveillance value. (PubMed, Am J Ophthalmol)

Positive plasma ctDNA reflected the presence of metastases. The ctDNA could be used as a complement or alternative to tissue sequencing. High VAF ctDNA might indicate rapid disease progression in distant metastasis patients.

27 days ago

Journal • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • NF1 mutation

28d

Follicular cell-derived thyroid carcinomas harboring novel genetic BRAFNON-V600E mutations: real-world data obtained using a multigene panel. (PubMed, Arch Endocrinol Metab)

EGFR gene mutations were found in 16 (29%) and KRAS or NRAS alterations in 8 (14%) of the 54 tumors analyzed. We described herein seven non-hotspot/novel variants in the BRAF gene, highlighting their potential role in expanding our understanding of FCDTC genetics.

28 days ago

Journal • Real-world evidence • Real-world

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)

BRAF V600E • KRAS mutation • EGFR mutation • BRAF G469E • NRAS A59 • BRAF G464E • BRAF T599

28d

ZWI-ZW25-201: A Safety and Efficacy Study of ZW25 (Zanidatamab) Plus Combination Chemotherapy in HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer (clinicaltrials.gov)

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Trial primary completion date: Aug 2024 --> Jul 2025

28 days ago

Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)

HER-2 amplification • HER-2 expression • KRAS wild-type • BRAF wild-type • NRAS wild-type

Avastin (bevacizumab) • cisplatin • gemcitabine • 5-fluorouracil • capecitabine • oxaliplatin • leucovorin calcium • zanidatamab (ZW25)

30d

Survival of Patients with Metastatic Melanoma Treated with Ipilimumab after PD-1 Inhibitors: A Single-Center Real-World Study. (PubMed, Cancers (Basel))

In case of failure to enroll patients in innovative clinical trials, second-line ipilimumab still represents an effective therapy in patients with metastatic wildtype melanoma and in the absence of brain metastases.

30 days ago

Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

BRAF mutation • NRAS mutation • BRAF wild-type • NRAS wild-type

Yervoy (ipilimumab)

Ancestry and somatic profile predict acral melanoma origin and prognosis. (PubMed, medRxiv)

We highlight novel low-frequency drivers, such as SPHKAP , which correlate with a distinct genomic profile and clinical characteristics. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.

1 month ago

Journal

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NF1 (Neurofibromin 1)

BRAF mutation • KIT mutation

Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules. (PubMed, Endocrinol Metab (Seoul))

Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules. Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

1 month ago

Journal

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) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RAS (Rat Sarcoma Virus) • DICER1 (Dicer 1 Ribonuclease III) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked)

BRAF mutation • PIK3CA mutation • TERT mutation

Mutation-Specific CRISPR Targeting with SaCas9 and AsCas12a Restores Therapeutic Sensitivity in Treatment-Resistant Melanoma. (PubMed, CRISPR J)

Two frontline BRAF inhibitors (BRAFi), vemurafenib and dabrafenib, are frequently used to treat unresectable or metastatic BRAF V600E melanoma. Our data support the feasibility of the development of CRISPR-Cas therapeutic approaches to the treatment of melanoma. Successful therapeutic CRISPR-directed gene editing would enable both specific and efficient editing of a mutation-specific targeting approach eliminate concern for on- and off-target damage to the genomes of healthy cells.

1 month ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog)

BRAF V600E • NRAS mutation • BRAF V600 • NRAS Q61K • NRAS Q61

Zelboraf (vemurafenib) • Tafinlar (dabrafenib)