RAS mutation

Multivariable Cox regression analysis revealed that K-RAS mutation (HR 3.345, p=0.017), N2 lymph node involvement (HR 2.458, p=0.015), and RSP localization (HR 0.338, p=0.001) were independently associated with poor survival.This study demonstrates that right-sided tumor localization, K-RAS mutation, and N2 lymph node involvement are key predictors of poor survival following SIRT in mCRC patients. RSP tumors, with distinct molecular and clinical profiles, exhibit shorter median OS and PFS after SIRT compared to LSP tumors.

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, p70S6K 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 of these combinations.

Targeting M-RasQ71R binding interface with optimized K-Ras inhibitor and cyclophilin A appears an alternative approach. Collectively, Ras allosteric mechanistic scenarios shape their personalities, function, and likely drug discovery.

Collectively, these results indicated that Casticin suppresses and sensitizes non-small-cell lung cancer cells to EGFR-TKIs. Casticin may serve as a sensitizing agent by targeting SMYD2 to improve the efficacy of EGFR-TKIs.

Following the development of resistance, all patients received platinum-based doublet chemotherapy plus immunotherapy; in the second-line setting, median PFS was modestly longer in the co-mutation groups compared with the single-mutation group (EGFR/TP53: 5.2 months; EGFR/KRAS: 5.0 months; EGFR single mutation: 3.9 months; overall log-rank P < 0.0001), with no significant difference between the TP53 and KRAS subgroups (P = 0.174). These associations were evident on Kaplan-Meier curves (with numbers at risk) and log-rank testing, and were supported by multivariable Cox models adjusted for age, sex, smoking history, clinical stage, histology, and ECOG performance status.

dMMR/MSI-H mCRC is an entity with different tumor biology. We consider that dMMR/MSI-H mCRC patients with BRAF wild, MCS and subsequent IO have better outcomes with 1st line 5FU-based treatment with anti-VEGF/anti-EGFRs.

Here we show that the BET inhibitor PLX51107 potently suppresses the growth of NRAS -mutant AML cell lines, and that these activities are enhanced by co-treatment with the MEK inhibitor PD0325901. AMLs that relapsed after frontline chemotherapy showed similar transcriptional remodeling. These studies demonstrate transcriptional plasticity in primary AMLs that relapse following in vivo treatment with either targeted agents or chemotherapy, and support evaluating BET inhibition in leukemias with monocytic differentiation and RAS mutations.

In this cohort, BRAF -mutant AML patients had poor overall survival with currently available treatments, including venetoclax-based regimens...Single-cell multiomic profiling revealed unique co-mutation patterns and immunophenotypes that highlight RAS pathway addiction and nominate BRAF -mutated disease as a distinct subtype within RAS pathway-aberrated leukemias. Drug sensitivity screens suggest broad CDK or HSP90 inhibition in addition to BRAF/RAS-directed inhibition may be effective targeted therapies in this prognostically poor AML subtype.

WT1 overexpression and KIT mutations (in selected cytogenetic contexts) are validated as adverse prognostic indicators in pediatric AML. Conversely, FLT3-ITD and CEBPA mutations require nuanced interpretation due to variable effects and methodological heterogeneity. These findings support the integration of molecular profiling into pediatric AML risk stratification and underscore the need for harmonized, prospective studies to refine prognostic models in this population.

Risk prediction of chemotherapy-associated VTE is a compelling challenge in oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Patients with a single type of metastatic cancer with a high risk of VTE will be selected for study inclusion. For the first time in ambulatory prophylaxis of cancer-associated thrombosis, a precision medicine approach will be used in a clinical trial. If the individualization of antithrombotic prophylaxis can reduce the complications of outpatient cancer treatment and be cost effective, it would be of great value in the future care of patients with metastatic CRC.

This retrospective study included 287 RAS-mutant mCRC patients, all of whom received at least three cycles of chemotherapy combined with bevacizumab...NHHR may serve as a potential prognostic biomarker in patients with RAS-mutant metastatic colorectal cancer. Its putative role in promoting tumor progression through modulation of chronic inflammation warrants further investigation.

Preoperative ctDNA is prognostic for early recurrence and overall survival after local liver treatment in patients with initially unresectable CRLM and KRAS/NRAS/BRAF mutated primary tumors. Further research should determine how to incorporate this parameter into clinical risk scores and therapy management.