KRAS G13D

USP15 acts as a critical mediator of oncogenic KRAS-driven metabolic reprogramming in NSCLC by promoting glycolysis via the TGF-β/SMAD signaling cascade. These findings uncover a previously unrecognized role of USP15 in linking metabolic regulation to tumorigenic signaling in KRAS-mutant NSCLC and suggest that targeting USP15 may represent a promising therapeutic strategy for this aggressive cancer subtype.

This study suggests codon 13 KRAS mutations may be associated with LR in LARC. However, given the small number patients and events, these findings should be cautiously interpreted until confirmed by larger studies. Preoperative genetic testing for KRAS mutations is suggested to enhance risk stratification.

Molecular docking and MD simulations confirmed strong and stable interactions with CDK6 and KRASG13D proteins. In vivo, 8b exhibited significant tumor growth inhibition in multiple murine models (up to 89.58 % TGI in EAC) with minimal systemic toxicity and favorable pharmacokinetic parameters.

OxaliTEX (NOVO-111) is a novel gadolinium(III) texaphyrin-platinum(IV) complex that is under development for clinical trials. This suggests that other factors, such as the slow plasma terminal phase of the free Pt(II) species from oxaliTEX that prolongs exposure to low drug concentrations, may contribute to the favorable in vivo antitumor activity and therapeutic index of the conjugate. These characteristics demonstrate superiority of oxaliTEX and generate much optimism for its success in future clinical trials.

KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.

Sensitivity to mutant-specific inhibitors largely overlapped with sensitivity to state-selective agents, suggesting that most RAS-mutant tumors will respond poorly to any currently available RAS inhibitor. Implications: Determining the signaling inhibition index (SII) can inform the design and clinical application of RAS-targeted therapies to improve tumor selectivity and therapeutic outcomes.

Here we present GoDig-LiF, which uses spectra and retention times predicted by the Prosit-TMT model in place of data libraries, enabling targeted proteomics with only a tandem mass tag-labeled sample, target list, and mass spectrometer. We applied GoDig-LiF to the quantification of mutated proteins in cancer cell lines, including KRAS G13D.

This study highlights the usefulness of ddPCR as a prospective clinical tool in oncology and liquid biopsy using blood cfDNA. It can be considered a better alternative to tissue biopsies and mutation profiling of candidate genes, particularly those that are linked to therapeutic response to TKIs.

In our case, it is found to have a G13D mutation in the KRAS gene and a novel RPSAP52-HMGA2 fusion. Though, the clinical significance of these alterations is yet to be proven, it may help to better understand this entity.

We found that KRAS-mutant CRC cell lines were sensitive to the RAS(ON) multiselective RAS inhibitor RMC-7977, given that treatment resulted in RAS-RAF-MEK-ERK pathway inhibition; halted proliferation; and, in some cases, induced apoptosis...Our findings demonstrate the power of reporter-assisted screening together with single-cell analyses for dissecting the complex landscape of therapy resistance. The strategy offers opportunities to develop clinically relevant combinatorial treatments to counteract the emergence of resistant cancer cells.

The predictions accurately reproduced the experimental data on KRAS allostery and provided a detailed map of allosteric communications mediated by the central β-sheet region of KRAS that connects the binding interface hotspots with allosteric hubs transmitting functional conformational changes. Together, these findings advance our understanding of mechanisms underlying allosteric regulation of KRAS binding and underscore the importance of targeting mutant-specific conformations for therapeutic interventions.

In most co-mutated models, regardless of the type of KRAS alteration, combination of inavolisib with MAPK pathway inhibitors showed synergy in vitro and in vivo. Our work highlights how specific codon substitutions in KRAS differentially toggle pathway activity and alter sensitivity to inavolisib, which could inform whether patients would benefit more from single-agent inavolisib or combination with MAPK pathway inhibitors.