KRAS G12D

Collectively, our findings suggest that the combination of DT2216/everolimus potentiates the anti-tumor efficacy of MRTX1133 associated with enhanced apoptosis induction and inhibition of compensatory survival signaling.

Together, these findings demonstrate that KRAS mutational context in pancreatic ductal epithelial cells shapes early transcriptional reprogramming that actively remodels nuclear architecture and nuclear sub-compartments. This work establishes nuclear structural remodeling as a structural state of KRAS-driven epigenetic dysregulation during PDAC initiation.

Indeed, we found KPA cells were more sensitive to hydrogen peroxide and diethyl maleate-induced oxidative stress as compared to KP and KPS cells. Together, these results indicate that PIK3CA is not required for lung cancer cell growth induced by mutant KRAS in vitro but is essential for in vivo progression and growth.

Furthermore, we address the difficulties with KRAS therapy, and the potential future directions needed to overcome them. An in-depth current literature review was done along with a review of the active clinical trials for KRAS-targeted therapeutics involving GI malignancies.

P2, N=60, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting

To explore this, we conducted a drug repurposing screen and identified three HIF1α inhibitors (bakuchiol, BAY-87-2243, 2-methoxyestradiol) whose sensitivities were correlated with sensitivity to Deltarasin, a KRAS inhibitor. Our findings suggest that HIF1α inhibitors could be used to sensitize PDAC to radiotherapy and KRAS inhibitors.

To investigate the mechanisms leading to valve loss, we combined the lymphatic-specific and tamoxifen-inducible Flt4CreERT2 with Kras-loxP-stop-loxP-G12D (Kras+/G12D) mice and Prox1GFP reporter mice to induce the restricted expression of KRAS-G12D and enable valve quantification in postnatal pups...We conclude that hyperactive KRAS signaling upregulates MMPs that become excessively activated by the upregulation of the PA pathway. MMPs then degrade the lymphatic valve ECM core, preventing valve formation.

Rectal cancer recurrence remains a major therapeutic challenge, particularly in patients unresponsive to conventional regimens. While previous studies have demonstrated limited benefit of immunotherapy in this tumor subtype, the present findings suggest an emerging therapeutic opportunity that warrants prospective evaluation to confirm efficacy, explore the mechanistic basis, and identify biomarkers predictive of durable response beyond the absence of liver metastases. More effective combinatorial regimens like zanzalintinib and atezolizumb (STELLAR-303) trial, as well as newer generation of CTLA-4 inhibitors like botensilimab, vilastobart, and muzastotug are showing more promise for patients with MSS colorectal cancers in particular who do not have liver metastases (NLM).

Ultrasound-stimulated CRISPR-CuNPs provide a potent, non-radiotoxic platform for targeted gene therapy. By integrating experimentally validated ultrasound parameters with KRAS gene silencing and curcumin-driven epigenetic activation of TP53 and PTEN, this approach achieves synergistic suppression of metastatic pulmonary cancer phenotypes. While sequencing-based genome-editing confirmation and long-term genomic stability studies remain necessary, this system holds significant promise for gene-enhancing, minimally invasive therapeutic strategies for the unborn.

MEX3A contributes to colorectal carcinogenesis, in association with PPARγ signalling modulation, impacting tumor development and therapeutic response.

Setidegrasib was associated with antitumor activity and a low incidence of treatment discontinuation due to adverse events in patients with previously treated advanced KRAS p.G12D-mutated NSCLC or pancreatic ductal adenocarcinoma. (Funded by Astellas Pharma; ClinicalTrials.gov number, NCT05382559.).

The pan-RAS mRNA vaccine demonstrates structural stability and strong immunogenic potential for PDAC. Synergistic immune activation with R848 may enhance anti-tumor efficacy, warranting experimental validation and toxicity assessment for clinical translation.