Regardless of the therapeutic effect of class I BRAF inhibitors such as vemurafenib, dabrafenib and encorafenib, melanoma patients with BRAF non-V600/RAS mutations remain limited response...The effect of PHI-501 on anchorage independent growth and cell proliferation compared to vemurafenib or belvarafenib (pan-RAF inhibitor) were tested in A375 (BRAFV600E), C8161 (BRAFG464E) and SK-MEL-2 (NRASQ61R) melanoma cell lines by soft agar assay, western blot and FACS analysis... PHI-501, a novel pan-RAF inhibitor, has potent oral anti-tumor activity. Melanoma cells harboring BRAF non-V600/NRAS or BRAF common V600E mutations exhibited significantly reduced proliferation, increased apoptosis and inhibited migration upon treatment with PHI-501. The results of this study suggest that PHI-501 has a potential to overcome the limited response in the treatment of melanoma, and warrant evaluation of PHI-501 as a single agent to treat both BRAF-and NRAS-mutated metastatic melanoma.

Long-term therapy with dabrafenib (BRAF inhibitor), cobimetinib or trametinib (MEK inhibitor) led to the establishment of the drug-resistant SK-MEL-3 (BRAF V600E) and SK-MEL-30 (NRAS Q61K) melanoma cell line. PHI-501 demonstrated potent growth inhibition (GI50 <1 µM) in seven melanoma cell lines harboring BRAF V600E or NRAS mutations. Melanoma cells resistant to RAF or MEK-targeted treatments or harboring NRAS mutation exhibited strong antiproliferative activity when treated with PHI-501, a highly potent pan-RAF/DDR dual inhibitor. The results of this study suggest that PHI-501, as a single agent, has the potential to overcome the restricted response in the treatment of melanoma.

The preclinical evaluation of PHI-501, a novel N-RAS inhibitor, showed clear evidence of anticancer activity for AML and improved efficacy in both in vitro and in vivo models. Consequently, PHI-501 is a new potent multi-kinase inhibitor with characteristics that warrant entry into human trials for the treatment of AML in patients expressing the N-RAS activating mutation.

Risk score-related DEGs were found enriched in ECM-receptor interaction and focal adhesion pathways. The five FRGs in BALF can be used for prognostic prediction in IPF, which may contribute to improving the management strategies of IPF.

miR-145-5p improves the sensitivity of acquired gefitinib-resistant cells to gefitinib via inhibiting NRAS and MEST expression. The miR 145-5p-NRAS/MEST axis in NSCLC provides insights for the development of a NRAS/MEST targeting therapeutic approach to overcome gefitinib resistance in NSCLC patients.

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Nevertheless, results from clinical trials are still prelaminar. A greater comprehension of the biology and intracellular interactions of NRAS-mutant melanoma will outline novel impactful strategies which could improve prognosis of these subgroup of patients.

The prevalence of NRAS mutations in primary nodular cutaneous melanoma cases from Indonesia is consistent with previous studies and is significantly associated with increased lymph node metastases. However, the predominant mutation detected in exon 2 (G12) is different from previous studies conducted in other countries. This suggests that melanoma cases in Javanese people have different characteristics from other ethnicities.

We report the NRAS mutation is common in cutaneous RDD, and NRAS A146T was the most frequent mutation in this cohort. Mutations in the NRAS gene can activate the RAS/MAPK signaling and have been reported to be associated with various cancers. It indicates that NRAS mutation in MAPK/ERK pathway may involve the pathogenesis of cutaneous RDD.

qPCR validation included selected 23 protein coding genes, 9 miRNAs and 3 lncRNAs involved in regulation of MAPK signaling pathway. Conclusion Future analysis of identified GLI target genes in melanoma cell lines with different mutation background will bring new insights into HH-GLI and MAPK signaling interplay and potentially lead to development of combined therapy with HH-GLI and BRAF/NRAS inhibitors.

qPCR validation included selected 23 protein coding genes, 9 miRNAs and 3 lncRNAs involved in regulation of MAPK signaling pathway. Conclusion Future analysis of identified GLI target genes in melanoma cell lines with different mutation background will bring new insights into HH-GLI and MAPK signaling interplay and potentially lead to development of combined therapy with HH-GLI and BRAF/NRAS inhibitors.

qPCR validation included selected 23 protein coding genes, 9 miRNAs and 3 lncRNAs involved in regulation of MAPK signaling pathway. Conclusion Future analysis of identified GLI target genes in melanoma cell lines with different mutation background will bring new insights into HH-GLI and MAPK signaling interplay and potentially lead to development of combined therapy with HH-GLI and BRAF/NRAS inhibitors.

qPCR validation included selected 23 protein coding genes, 9 miRNAs and 3 lncRNAs involved in regulation of MAPK signaling pathway. Conclusion Future analysis of identified GLI target genes in melanoma cell lines with different mutation background will bring new insights into HH-GLI and MAPK signaling interplay and potentially lead to development of combined therapy with HH-GLI and BRAF/NRAS inhibitors.

Our data suggest that [I]ICF01012-TRT and MEKi combination could be of benefit for advanced pigmented BRAF-mutant melanoma care and that [I]ICF01012 alone could constitute a new potential NRAS-mutant melanoma treatment.

The rarity of this tumor further evokes an interest in this case. A better understanding of the disease warrants a review of more cases with longer follow-ups.

The latest evidences are here reviewed, providing also an overview of the real-world RAS mutation testing practice across different Italian laboratories. On this basis, we propose a knowledge-based system, www.rasatlas.com, to support the healthcare personnel in the management of patients featuring RAS gene mutations in the landscape of precision oncology.

Therefore, let-7c may be considered to be an anti-oncogene of LIHC. The present study may provide novel targets and strategies for the diagnosis and treatment of LIHC.

A comprehensive review of the literature was performed using the keywords "conjunctival melanoma", "immune checkpoint inhibitors", "BRAF inhibitors", "MEK inhibitors", "CTLA4 inhibitors", "PD1 inhibitors", "c-KIT mutations", "BRAF mutations", "NRAS mutations", "dabrafenib", "trametinib", "vemurafenib", "ipilimumab", "pembrolizumab", and "nivolumab". Furthermore, immune checkpoint PD-1 and CTLA4 inhibitors with favorable clinical outcomes in the treatment of cutaneous melanoma have increased recurrence-free survival and reduced metastatic spread in CM cases. The complex molecular mechanisms that contribute to the development of CM can be targeted both by molecular inhibitors of oncogenic pathways as well as immune checkpoint inhibitors in order to halt progression of the disease and increase survival.

Treatment strategies include laser therapy, chemical peeling, dermabrasion, and surgical removal/grafting for CMNs and shunt surgery and surgical removal/chemo/radiotherapy for CNS lesions. Biologically targeted therapies tailored (a) BRAF/MEK in NCM mice (MEK162) and GCMN (trametinib); (b) PI3K/mTOR (omipalisib/GSK2126458) in NMC cells; (c) RAS/MEK (vemurafenib and trametinib) in LCMNs cells; or created experimental NMC cells (YP-MEL).

BRAF inhibitor-resistant cells develop a range of 'escape routes', so multiple different treatment targets will probably be required to overcome resistance. In the future, it may be possible to personalize combination therapy towards the specific resistance pathway in individual patients.

Our results indicated that miR-145 is an important tumor suppressor and the inhibitory strategies against N-RAS/VEGF signaling pathway might be potential therapeutic applications for UM in the future.

By a modified capture hybridization (CHART) analysis of the protein targets, we uncovered interactions of Morrbid lncRNA with the SFPQ (splicing factor proline and glutamine rich)-NONO (non-POU domain-containing octamer-binding protein) splicing complex. Finally, we propose the regulation mechanism of NRAS splicing in murine hepatocytes by alternative splicing coupled with the NMD pathway with the input of Morrbid lncRNA.

BRAF mutations are more frequent among PoSA patients, and this seems to be a continuous trend. PrSA and PoSA patients seem to present a distinct profile from SA, including differences in molecular and pathologic aspects. These findings could impact the frequency of screening tests among different age groups.

In addition, the promotion of OS progression by hsa_circ_000007 was blocked by miR-145-5p and miR-151-3p-mediated NRAS inhibition. In conclusion, hsa_circ_0000073 facilitated the proliferation, migration, invasion and MTX resistance of OS cells through the inhibition of miR-145-5p and miR-151-3p-mediated downregulation of NRAS.

In the wt/wt population, 35 pts received ipilimumab, 131 antiPD-1or antiPD-L1 and 2 the combination of both...Legal entity responsible for the study: The authors. Funding: Has not received any funding.

Their pharmacogenomic role, already defined in colorectal cancer, is under investigation in LARC with promising results concerning specific somatic mutations in KRAS and TP53, as predictors of tumor response and prognosis. The availability of circulating tumor DNA in plasma may also represent an opportunity to monitor somatic mutations in course of therapy.

These results provide the first evidence that NRAS oncogenic variant was identified in DNA samples from KLA patients from not only two affected lesions but also plasma and pleural effusion.

This compound reduces cell growth in NRAS-driven versus non-NRAS-driven melanoma lines and inhibits tumor progression in an NRAS-mutated melanoma xenograft mouse model. Our work demonstrates that AMD can effectively suppress NRAS activity and could represent a promising new avenue for discovering lead com-pounds for treatment of NRAS-driven cancers.

Our results indicated that miR-145 is an important tumor suppressor and the inhibitory strategies against N-RAS/VEGF signaling pathway might be potential therapeutic applications for UM in the future.

This conclusion was supported by significantly reduced expression of selected NF-κB-dependent genes: cyclin D1 (CCND1), C-X-C motif chemokine ligand 8 (CXCL8), and vascular endothelial growth factor (VEGF), as shown at transcript and protein levels, as well as secretion of IL-8 and VEGF. Our study indicates that 17-aminogeldanamycin can be used for efficient inhibition of NF-κB activity and the simultaneous diminution of IL-8 and VEGF levels in the extracellular milieu of melanoma.

One squamous cell carcinoma with a BRD4/NUTM1 fusion treated with cisplatin/vinorelbine and atezolizumab prior to implant. Eight glioblastomas (prior temozolomide=3 (37%), MGMTmt=5 (62%) and IDHm=1 (12%)... The importance of PDX development programs relies on the reproducibility of tumors with specific oncogenic drivers potentially targetable. A full comprehensive characterization of PDX shareable collections are paramount for tracking of molecular, diagnostic, prognostic and predictive markers of drug response.

Legal entity responsible for the study The authors. Funding BMS.

This information implied the immune-related properties of the 12-gene signature. Our study emphasizes the significance of the gene expression signature in that it may be an indispensable prognostic predictor in melanoma and has great potential for application in personalized treatment.

Chelidonine suppresses NRAS-mutant cancer cell growth and could have utility as a new treatment for such malignancies.

Human KRAS/NRAS/BRAFV600-wildtype colorectal cancer cell lines with NF1 mutations displayed reduced NF1 mRNA or protein expression and were resistant to EGFR blockade by gefitinib or cetuximab. Loss of NF1 may be a useful biomarker to identify patients that are less likely to benefit from single agent anti-EGFR therapy in CRC and may direct potential combination strategies. Implications: This study suggests that further clinical validation of NF1 status as predictor of response to anti-EGFR targeting antibodies in CRC patients with KRAS/NRAS/BRAFV600-wildtype tumours is warranted.

The mutation of NRAS gene has no effect on the prognosis of AML patients.

Taken together, in CRPC, let-7b blocks the Ras/Rho signaling pathway by inhibiting NRAS expression, thereby inhibiting cell proliferation and invasion and promoting cell apoptosis. Thus, let-7b targeting NRAS may be a potential therapeutic target for the repression of CRPC.

Activated KRAS was sufficient to cause resistance to combined MEK/CDK inhibition and to replace genetic depletion of oncogenic NRAS. In summary, our comprehensive functional genetic screening approach revealed modulation of resistance to the inhibition of MEK1/2, CDK4/6 or their combination in NRAS-mutant melanoma.

Besides that, SNHG16 could regulate NRAS expression through competitively binding to miR-183-5p in RB cells. NRAS functioned as an oncogene to contribute to RB progression by SNHG16/miR-183-5p/NRAS regulatory network, indicating a novel and promising therapeutic target for RB.