NRG1 mutation

ERK1/2 (ulixertinib and SCH772984), MEK1/2 (binimetinib), and PI3K (pictilisib) inhibitors inhibited growth of RRAS Q87L or RRAS2 Q72L cells more potently than cells expressing wildtype proteins. Oncogenic R RAS/RRAS2 mutations were detected in LUAD at a rate similar to some other well-characterized lung cancer drivers, such as HRAS/NRAS hotspot mutations or NRG1 fusions. Our study supports the inclusion of RRAS /RRAS2 into routine molecular diagnostic protocols for precision oncology and clinical development of pan-RAS inhibitors, such as RMC-6236, for patients with these driver mutations in order to fully realize the potential benefit of RAS-targeted therapies.

High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.

High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.

Cell-type-specific loss-of-function studies indicate that nrg1 type II is required in Rohon-Beard neurons to signal to other neurons, not oligodendrocytes, to modulate spinal cord myelination. Together, our data support a model in which unmyelinated neurons express Nrg1 type II proteins to regulate myelination of neighboring neurons, a mode of action that may coordinate the functions of unmyelinated and myelinated neurons in the CNS.

Current treatments include surgery, tyrosine kinase inhibitors (e.g. sorafenib, pazopanib, sunitinib), and NSAIDs while gamma secretase inhibitors are under study. A large cohort of 204 desmoid-type fibromatosis samples analysed by targeted next-generation sequencing at the University Munster revealed imatinib sensitive KIT V559D in addition to AKT1, ALK, EGFR and ERBB2, however, NRG1 and MAFB were not included in the gene panel. Copy number alterations and mutations in NRG1 and MAFB may be relevant to the pathogenesis and a potential targeted therapy of desmoid fibromatosis. Copy number alterations and mutations in NRG1 and MAFB may be relevant to the pathogenesis and a potential targeted therapy of desmoid fibromatosis. Further analyses will be needed to confirm the relevance of these genes. Larger studies that include copy number analysis, whole exome and RNA sequencing are warranted.

Among histology-agnostic therapies, pembrolizumab or dostarlimab demonstrated comparable activity in MSI metastatic colorectal cancer (mCRC) as in other tumors with MSI status (ORR 38% vs 40% and 36% vs 39%, respectively), while entrectinib or larotrectinib proved effective in NTRK rearranged mCRC even though less dramatically than in the overall population (ORR 20% vs 57%, and 50% vs 78%, respectively). Targeting of ERBB2 mutations and NRG1 fusion provided discrepant results. In conclusion, agnostic targets such as MSI and NTRK fusions are already exploitable in mCRC, while the plethora of emerging histology-tuned targets represent a challenging opportunity requiring concurrent evolution of molecular diagnostic tools.

Conclusions : Primary and metastatic prostate cancers contain differently shared genetic aberrations. In metastatic prostate cancer, UGT1A1 , NRG1, and FANCA were distinctively mutated compared with primary prostate cancer, suggesting promising target for metastatic prostate cancer therapy.

Research continues at a rapid pace, with a number of phase III trials underway to fully evaluate new promising agents under development for improving outcomes in patients with NSCLC harboring distinct molecular subtypes. This review will provide a comprehensive summary of existing data as well as a user-friendly guide on the current status of novel targeted therapy in oncogene-driven advanced NSCLC.

This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.

This is the largest molecular study of IMAs to date, where we demonstrate the presence of a major oncogenic driver in nearly all cases. This study is the first to document more aggressive characteristics of NRG1-rearranged IMAs, ERBB2 as the third most common alteration, and a novel NRG2 fusion in these tumors. Comprehensive molecular testing of KRAS wild-type IMAs that includes fusion testing is essential given the high prevalence of alterations with established and investigational targeted therapies in this subset.

First-line and second-line chemotherapy does improve quality of life and OS in the metastatic setting, FOLFIRINOX and gemcitabine + nab-paclitaxel being the two current standard first-line options. Molecular profiling of metastatic patients is emerging, as some personalised therapies are possible for rare subtypes such as MSI high, BRCA1-2 mutated and NRG1/NTRK fusion gene PA.