RAS mutation

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.

Nevertheless, the primary public health priority pertains to the prevention of AA exposure. Further epidemiological and mechanistic studies are urgently needed.

Depending on the Bethesda category, the positive predictive value for malignancy of the seven-gene panel ranged between 18.18% (Bethesda III) and 91.07% (Bethesda V), while the negative predictive value ranged between 93.92% (Bethesda III) and 24.14% (Bethesda V). In conclusion, molecular testing with the seven-gene panel can improve ROM estimation in cytopathologically indeterminate thyroid nodules, but its clinical utility depends on the detected gene alteration.

In the absence of BAMPs, cells carrying oncogenic KRAS mutations are unable to attain their full penetrance in proliferation. Overall, this work unveils the long-overlooked role of branched actin-driven cell morphology in the functionalization of KRAS mutants as potent oncogenes.

Mutant-specific KRAS G12C inhibitors have shown promising therapeutic efficacy, leading to FDA approval of sotorasib and adagrasib, although their use is limited to patients with the relatively rare G12C KRAS mutation...While just a few years ago, pan-RAS inhibitors were predicted to be severely toxic or even fatal, the apparent safety profile of RMC-6236 (daraxonrasib), a pan-RAS inhibitor currently in clinical trials, suggests otherwise. Indeed, pan-RAS inhibitors are now considered by many in the RAS field to be the most promising class in development. In this review, we summarize the evolution and current status of pan-RAS and pan-KRAS inhibitors in preclinical and clinical development and highlight emerging human-relevant tumor models that are advancing preclinical evaluation.

In EOCRC, clinical and treatment-related factors remained independently associated with overall survival after adjustment for disease stage, whereas the evaluated genetic variables did not retain statistical significance. These findings highlight the importance of clinical management strategies, while the prognostic value of genetic alterations requires further investigation.