KRAS mutation

Notably, MAP2K1 E102-I103 deletion was frequently observed in pre-invasive samples, which endowed alveolar type II cells with increased growth potential and initiated tumor formation, suggesting that it is a potential driver mutation of LUAD. In summary, our study highlights key molecular changes during the stepwise progression of LUAD, provides insights into the identification of novel therapeutic targets, and helps to define the curative time window for this disease.

Garsorasib demonstrated encouraging antitumor activity and a tolerable safety profile in patients with KRAS G12C-mutated advanced pancreatic cancer.

Their ability to disrupt oncogenic signaling, overcome resistance, and target cancer stem cells underscores their therapeutic potential. Future research should focus on pharmacokinetic refinement, toxicity profiling, and clinical validation to advance their application in precision oncology.

High infiltration of TILs correlated with improved OS and DFS, whereas BRAF and KRAS mutations were associated with worse OS in patients with localized dMMR/MSI-H CRC. These findings highlight the potential utility of biomarkers for improving prognostic assessment and personalizing management in dMMR CRC.

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.

Glecirasib monotherapy and its combination with cetuximab represent potential treatment options for patients with advanced, refractory colorectal cancer harbouring KRASG12C mutations. The promising efficacy and safety support further exploration of glecirasib-based combinations in earlier lines of treatment.

The age threshold for optimal differentiation between patients with EOLC and LOLC is 50 years, EOLC patients benefit from aggressive surgery and age-dependent treatment, supported by treatment efficacy and molecular heterogeneity.

Preclinical studies demonstrate that MEL enhances chemoradiotherapy efficacy-reducing tumor volume by 70% in murine colorectal models and decreasing 5-fluorouracil (5-FU) resistance via miR-532-3p/β-catenin axis modulation...Given its low toxicity and putative synergy with immunotherapies, MEL should be regarded as an adjunct under investigation rather than an established option; to date, no GI-specific phase III randomized trials exist, and clinical signals come primarily from small, heterogeneous cohorts. Dosing is unstandardized and limited by low oral bioavailability (first-pass) and possible pharmacogenomic variability.

Here, we show that sotorasib, adagrasib, and the RAS-ON inhibitor RMC-6291 are effective in a neuroblastoma cell line altered by KRAS(G12C). Importantly, sotorasib also decreased ERK phosphorylation in a NRAS(G12C)-altered cell line xenograft model; however, this treatment did not prolong survival as a single agent. These results suggest that combinations of targeted agents that include sotorasib may be required for clinical benefit in pediatric patients with H- or NRAS(G12C)-altered malignancies in addition to those with KRAS(G12C)-altered malignancies.

In KRAS-mut NSCLCs with or without STK11/KEAP1 mutations, the GPAs in the DNA-binding genes ARID1A/ARID2 affected the outcomes of immunotherapy, possibly through the downregulation of STING expression.

P1, N=27, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 --> Jun 2027 | Trial primary completion date: Aug 2025 --> Jun 2027

Lastly, we evaluate its feasibility for multi-cancer early detection in population-scale screening using pooled plasma samples. The EC-SNV-Seq assay can enable highly sensitive and specific identification of low-frequency mutations, facilitating early cancer diagnosis and personalized treatment strategies.