KRAS G12D

Molecular dynamics and NMR titration confirm the superior stability and binding affinity of the 10-mer. These results highlight how peptide length and conformation critically shape immune visibility, offering mechanistic insight for optimizing TCR-T therapies against elusive neoantigens like KRAS G12D.

Consistently, expression of IL-15 resulted in blockade of tumor progression in the TKP CCA model. These findings highlight the importance of oncogenic Kras in CCA tumor maintenance and underscore KRAS inhibition as a potential therapeutic approach for CCA.

This is the first report of trametinib-nintedanib for a 57-year-old KRAS G12D-mutated recurrent pancreatic ductal adenocarcinoma. He had transient remission (lower CA19-9, stable lesions) but died of gastrointestinal bleeding, showing efficacy and bleeding risk.

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.

Furthermore, combining an UBE2D3 small-molecule inhibitor with KRASG12D-specific TCR-T-cell therapy yields synergistic antitumor effects. Our findings reveal a negative feedback mechanism in which cancer cells, "camouflaging" themselves, evade IFN-γ-induced antigen presentation via UBE2D3 upregulation, highlighting a potential therapeutic target for enhancing antitumor immunity.

Lipid-laden stellate cells promote fibrosis, immunosuppression, and epithelial-mesenchymal transition. NAFPD may represent an early, modifiable PDAC niche, warranting further imaging-omic studies and targeted prevention trials.

However, patients with G12V mutations achieved significantly longer survival with fluorouracil-based than gemcitabine-based chemotherapy. These findings suggest that, while KRAS subtyping alone lacks prognostic value, the G12V subtype may inform chemotherapy selection and warrants further prospective validation.

P1/2, N=28, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1 --> P1/2

Remarkably, KU suppressed AKR1B1 and SORD expression, reduced intracellular sorbitol and fructose levels, and induced alterations in EMT-related proteins, such as ZEB1, E-cadherin, and vimentin, at a lower concentration than epalrestat (EP), a known AKR1B1 inhibitor...Collectively, these findings suggest that KU inhibits the aggressive phenotype of lung cancer by targeting the polyol pathway and modulating EMT processes. These results support its potential as a therapeutic candidate, highlighting the need for clinical evaluation in NSCLC patients.

In a human xenograft model, depletion of FBXO11 cooperated with AML1-ETO and mutant KRASG12D to generate serially transplantable AML. Our findings suggest that reduced FBXO11 cooperates to initiate AML by priming HSPC for myeloid-biased self-renewal through attenuation of LONP1-mediated regulation of mitochondrial respiration.

P1, N=9, Active, not recruiting, Chinese PLA General Hospital | Recruiting --> Active, not recruiting | N=15 --> 9 | Trial primary completion date: Dec 2025 --> Jun 2026

Based on mechanistic investigations, we propose that KRAS mutations impair intrinsic hydrolysis by disrupting the interactions needed to align the nucleophilic water molecule with GTP for nucleophilic attack. These results can assist small-molecule inhibitor design and also benefit the development of other therapeutic strategies, such as rescuing hydrolysis.