KRAS G12D

P1, N=210, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2033 --> Feb 2029 | Trial primary completion date: Jun 2031 --> Feb 2029

Additionally, molecular docking studies demonstrate a robust binding affinity of compound 10b with both KRASG12C and KRASG12D proteins. These findings provided unique pathways for investigating multi-target inhibitors aimed at mutated KRAS proteins, thereby advancing the development of innovative molecular therapies for cancers associated with KRAS mutations.

P1, N=681, Recruiting, Astellas Pharma Inc | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2027 --> Dec 2028

The patient underwent radical local wide resection 1 month later, and no recurrence or metastasis was observed during a follow-up period of 12 months. The present case report provides a real-world reference for the clinical diagnosis, selection of treatment plans and evaluation of the prognosis of painless PMA.

After carboplatin and paclitaxel treatment, a combination chemotherapy used in human LUSC, we detected increased neutrophils in circulation, spleen and tumors, and increased Bcl-xL in neutrophils and TANs. Bcl-xL blockade decreased the pool of Bcl-xL-high TANs and synergized with chemotherapy. Altogether, our results suggest distinct outcomes for targeting TANs in different tumor types and reinforce the concept of repurposing BH3 mimetics against cancer.

Mechanistically, loss of NSUN2 reduces ERK phosphorylation in Apc-deficient models, and oncogenic KrasG12D expression is sufficient to restore ERK signalling and rescue ISC expansion. Together, this establishes a novel role for NSUN2 as a key regulator of ISC-driven CRC initiation and describes a critical molecular mechanism linking m5C methylation to MAPK-driven stem cell transformation.

In addition, we identified previously undescribed cryptic pockets and validated select hits using computational chemistry and NMR spectroscopy. These pockets represent promising opportunities for future drug discovery campaigns.

An experimental PROTAC drug designed to degrade mutant KRASG12D produced tumor responses in patients with advanced non-small cell lung cancer and pancreatic ductal adenocarcinoma in a phase I trial, with limited toxicity. Investigators are now testing the therapy in combination regimens and later-stage studies as competition intensifies among companies developing drugs against the common cancer driver.

This study is the largest longitudinal analysis of KRASM testing conducted in Australia, with significant improvement in testing rates seen over the time period. Rates of KRASM and characteristics of Australian KRAS mt patients correspond with published literature.

P1, N=210, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

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.