NRAS G13

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.

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

We review reports of the interaction of cathepsin B with trypsinogen in the pancreas and caspases in inflammasomes and the potential effect of premature activation of trypsin on immune evasion of G12R mutants. We summarize our observations and literature review in a schematic describing the potential role inflammation and the actions of cathepsin B, trypsin, and caspases on the immune evasion of KRas and related Ras family gene products.

To our knowledge, after review of the available literature, this appears to be the first reported case of recurrent PHPT with synchronous ipsilateral parathyroid adenoma/hyperplasia and multifocal PTC comprising three histological variants with distinct molecular alterations. This unique presentation underscores the necessity for comprehensive thyroid evaluation in PHPT patients, the utility of molecular profiling in establishing tumor clonality, and the importance of individualized surgical planning in complex endocrine neoplasia.

Pediatric PDLM carries a uniformly poor prognosis. Immunotherapy and chemotherapy were the only treatments independently associated with improved survival, highlighting their central role in management of this rare disease.

Together, these effects bypass intrinsic effector selectivity, allowing canonical RAS to co-opt effectors normally associated with other RAS subfamilies and broaden downstream signaling. This framework explains how inherent effector preferences govern normal signaling and how oncogenic mutations override these constraints to expand effector engagement in RAS-driven cancers.

This case underscores the importance of early response evaluation in ICI-treated MSI-H tumors. Rapid disease progression requires prompt differentiation between HPD and pseudoprogression, emphasizing the necessity of timely therapeutic modification.

c-KIT mutations resulted in 35% of the children tested. The RT-PCR technique resulted more sensitive in finding c-KIT D816V, while NGS in detecting other mutations whose prognostic roles require further investigation.

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

BRAF V600E was detected in 3.7%.ConclusionsWe report a rise in EOCRC in Serbia, especially in ages 45-49, and recommend policy makers to lower the screening age to 45. We present the first detailed molecular profile of Serbian EOCRC and recommend that policy makers implement routine KRAS variant testing and ensure access to KRAS G12C-targeted therapies to improve personalized care.

Across a CRC panel that included SNU-C5/WT and its 5-fluorouracil- and oxaliplatin-resistant derivatives, HT-29 (KRAS-wild-type), and HCT-8 and LoVo (KRAS-mutant), co-immunoprecipitation showed that PrPC forms complexes with the 37/67 kDa laminin receptor (RPSA), with PrPC-RPSA association particularly increased in KRAS-mutant HCT-8 and LoVo cells. Taken together, these findings suggest that extracellular PrPC supports RAS-AKT signaling, proliferation, and tumor-associated angiogenesis in KRAS-mutant colorectal cancer, and that PrPC neutralization additively enhances 5-fluorouracil activity in KRAS-mutant models. The data provide a preclinical basis for evaluating PrPC antibodies in combination with fluoropyrimidine-based regimens in patients with KRAS-mutant CRC.

For patients receiving cytarabine-based front-line chemotherapy, those with RAS mutations had shorter median OS compared to RAS-wild-type AML (27.1 vs. 122.2 months, p < 0.001)...Although 80 (66.1%) of 121 total RAS mutations were found in codons G12 or G13, most substitutions were G12D or G13D, which are not targetable by commercial RASG12C inhibitors. This study sheds light on prognostic implications of RAS mutations and may inform extension of the therapeutic reach of RAS inhibitors to AML.