NRAS G12D

P1/2, N=158, Active, not recruiting, Elicio Therapeutics | Recruiting --> Active, not recruiting

Unexpectedly, the SNV-selective crRNAs harboring mismatched nucleotides reduce the promiscuous collateral activity of the RfxCas13d ortholog. These findings demonstrate that the CRISPR-Cas13 system can be reprogrammed to target mutant transcripts with single-base precision, showcasing the tremendous potential of this tool in personalized transcriptome editing.

We elucidated the mechanism of action of a potent KRAS G12D inhibitor, MRTX1133. Binding of this inhibitor to the switch-2 pocket causes a complete shift of KRAS G12D towards the "inactive" conformation and prevents binding of effector RAS-binding domain (RBD) at physiological concentrations, by signaling through an allosteric network.

These findings highlight the complex interplay between molecular subtypes, clinicopathological features, and survival outcomes in early CC. Further research is needed to elucidate underlying mechanisms and develop personalized treatment strategies.

While the effectiveness of MEK inhibitors such as selumetinib is established in NF1-associated inoperable plexiform neurofibromas, their use in managing hyperactive KRAS-driven epidermal nevi and hypertrophic neuropathy remains unproven, and this case, to our knowledge, is the first such case to be reported. Shared molecular dysregulation and overlapping clinical features between these conditions suggest potential for effective therapeutic application of MEK directed therapy to address a range of conditions resulting from germline and/ or mosaic expression of aberrantly regulated RAS signaling.

P1, N=100, Active, not recruiting, Black Diamond Therapeutics, Inc. | Recruiting --> Active, not recruiting

Human KMT2A-r AML cells could be pharmacologically sensitized to NKG2D-CAR T cells by treatment with the histone deacetylase inhibitor LBH589 (panobinostat) which caused upregulation of NKG2D-ligand levels...Finally, the results were validated and extended to acute leukemia in infancy. Combined, activating mutations induced mutation-specific changes in the epigenetic landscape, leading to changes in transcriptional programs orchestrated by specific transcription factor networks.

In our case series, more than 60% of patients had at least one mutation in KRAS, NRAS, or BRAF. The presence of mutations in these genes is closely related to CRC prognosis and helps define the best therapeutic approach in patients with metastatic CRC.

This cohort study found that KRAS allelic variants were relatively common and may be potentially actionable genomic alterations in patients with BTCs, especially perihilar cholangiocarcinoma and extrahepatic cholangiocarcinoma. The findings add to the growing data on genomic and immune landscapes of KRAS allelic variants in BTCs and are potentially of value to the planning of specific therapies for this heterogeneous patient group.

The study's findings indicate a rising frequency of mutations in these genes in Iran, highlighting the need to screening mutations in the main exons of all three genes for effective colorectal cancer treatment strategies.

RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.

Our data demonstrate that RAS mutations do not affect outcome in rego-treated patients as well as TFD/TPI-treated patients. Nevertheless, a trend toward a higher efficacy of rego in RAS-mutated (in particular codon 12, rare RAS mutations, and G12D) patients has been recorded. The rego-TFD/TPI sequence seems to be superior to the reverse sequence in patients carrying an RAS codon 12 mutation, although the impact of other factors as disease burden or performance status cannot be excluded.