RAS mutation

To determine combination partners that enhance RAS(ON) mutant-selective inhibition, a drug repurposing screen revealed that KRASG13C models are selectively vulnerable to chemotherapy. Combination of docetaxel with RMC-8839 demonstrated robust anti-proliferative activity in KRASG13C-driven NSCLC models in vitro and in vivo.

Furthermore, co-occurring RAS pathway mutations leading to increased wild-type RAS activation are enriched in codon 13 mutant tumors. Consistent with a role for wild-type RAS(ON) signaling, combination of RMC-8839 with a RAS(ON) multi-selective inhibitor resulted in deeper inhibition of KRAS G13C-mutant xenograft tumor growth than either inhibitor alone.

Our results demonstrate that tumour sidedness critically influences liquid biopsy interpretation in metastatic colorectal cancer, underscoring the need to incorporate the primary tumour location into the clinical assessment of circulating biomarkers.

In Saskatchewan, stage IV CRC survival is comparable between rural and urban patients; however, the care pathway is hindered by systemic therapy delays linked to rural diagnostic laboratory locations. While survival rates are currently similar, the delays associated with rural laboratory workups represent an actionable target for improvement.

MiR-31-3p is a promising predictive biomarker for cetuximab response in RAS wild-type mCRC, with low expression consistently associated with improved outcomes. However, tumor sidedness may modulate its predictive value. Prospective validation studies with standardized assays are needed before clinical implementation. Integration of miR-31-3p with existing markers could help identify patients unlikely to benefit from anti-EGFR therapy.

The Bethesda system provides high diagnostic accuracy for definitive cytological categories in pediatric thyroid nodules. Even indeterminate categories carry elevated malignancy risk, supporting careful surgical consideration and the value of BRAF V600E testing for preoperative risk stratification.

NRAS p.Q61R/K comprises 99% of reported NRAS variants. TERTp is the most frequent co-mutation. Among NRAS p.Q61R/K nodules, there are 2 different clusters of samples based on the activity of hallmarks of cancer pathways. Further studies correlating these clusters with clinical and pathological outcomes are necessary.

Co-expression network analysis highlighted disrupted transcriptional coordination in tumors. This work establishes a multidimensional epigenetic framework for PTC with combinatorial diagnostic signatures and condition-specific associations between DNA modifications and driver mutations (BRAF vs. RAS).

P1, N=24, Recruiting, Ruijin Hospital

In this cohort, BRAF-mutant AML patients had poor overall survival with currently available treatments, including venetoclax-based regimens. Drug sensitivity data suggest possible avenues for targeted treatment of BRAF-mutated AML.

Epidermal growth factor receptor (EGFR) blockade combined with cytotoxic chemotherapy has substantially improved outcomes in unresectable metastatic colorectal cancer (mCRC), particularly in patients with left-sided RAS wild-type disease [...].

Increasing age at the time of first-line therapy for advanced disease stage was associated with a statistically significant increase in the hazard of death (p = 0.031). In the advanced disease stage, RAS/BRAF wild-type colorectal cancers were significantly associated with a survival advantage.