NRAS mutation

DLI is an effective treatment strategy for post-transplant relapse of all myeloid malignancies, with specific genetic subtypes showing poorer outcomes and survival.

NF1 mutation is the strongest gene-level correlate of lung-selective metastasis in cutaneous melanoma. The NF1-mutant subtype may represent a dual-biomarker population and could warrant both pulmonary surveillance and prospective evaluation for immunotherapy.

The patient subsequently received etoposide plus cisplatin (EP), irinotecan, and third-line combination therapy of serplulimab, anlotinib, and temozolomide. Radical surgery combined with platinum-based chemotherapy constitutes the mainstay of treatment. Molecular testing can provide a basis for personalized therapy, and multiline comprehensive treatment may offer prolonged survival benefits for patients.

Flow cytometry antibody indicators can suggest that MDS patients are prone to gene mutations related to chromatin regulation, transcriptional regulation, poor prognosis and leukemia transformation. The proportions of CD25+ T cells and lymphocytes were both closely related to the T-bet and GATA3 gene mutations.

Moreover, FTY720 co-treatment resensitized G12D NRAS-mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70 S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS-mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy.

The inhaled P2-grafted nanochitosan provided a positive lung cancer recovery with reduced systemic exposure and hematological/biochemical toxicities. Single instead of dimethylation of YKWYYRGAA promoted the cascades of inter-dependent anti-cancer activities and efficacy of nanochitosan.

Pharmacological inhibitors of EZH2, including tazemetostat, have shown promise in preclinical melanoma models by restoring antigen presentation, enhancing CD8+ T-cell infiltration, and reversing transcriptional programs associated with immune resistance. This review aims to summarize the role of EZH2 in the molecular pathogenesis of ALM, emphasizing its contributions to epigenetic regulation, tumor plasticity, and immune escape, and discusses emerging therapeutic strategies targeting EZH2-mediated pathways to improve outcomes for this aggressive melanoma subtype.

This review synthesizes current knowledge on CMN epidemiology, molecular pathogenesis, diagnostic advancements, and therapeutic strategies. Future directions emphasize longitudinal studies to validate interventions, multidisciplinary collaboration, and biomarker-driven personalized management.

P2, N=216, Completed, Melanoma Institute Australia | Trial completion date: Dec 2025 --> Mar 2026

P3, N=590, Recruiting, Revolution Medicines, Inc. | N=420 --> 590

The IR group displayed a heterogeneous genomic profile, with NRAS/KRAS, Ph-like mutations and delCDKN2A/CDKN2B among the most frequent alterations. These observations highlight the potential of integrated genomic profiling to refine risk stratification, particularly by identifying clinically relevant subgroups within the IR category.

Patients treated with venetoclax plus intensive chemotherapy (Ven+IC) showed the best composite complete remission (CRc) rate and OS compared to intensive chemotherapy, venetoclax plus reduced-intensive chemotherapy, and reduced-intensive chemotherapy (CRc rate: 89.5% vs. 62.4% vs. 57.3% vs. 61.4%; median OS: not reached vs. 39.9 months vs. 34.8 months vs. 12.7 months). Multivariate analysis identified multiparameter flow cytometry minimal residual disease negativity post-induction therapy, allogeneic hematopoietic stem cell transplantation, and Ven+IC as independent favorable prognostic factors for event-free survival (EFS), and KMT2A::MLLT4 fusion, EVI1 overexpression were independent unfavorable prognostic factors for EFS. In summary, our study showed characteristics and prognostic implications in newly diagnosed KMT2Ar AML in China.