KRAS mutation

P2, N=29, Not yet recruiting, Roswell Park Cancer Institute

P3, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Sep 2026 | Trial primary completion date: Feb 2026 --> Aug 2026

P3, N=400, Not yet recruiting, Hoffmann-La Roche

P2, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2026 --> Nov 2027

P1, N=48, Not yet recruiting, Kumquat Biosciences Inc.

Mechanistically, galangin suppressed M2 macrophage polarization, directly interacted with the efferocytosis-related targets CAMK2A and MERTK, and reduced their expression. Together, these findings establish efferocytosis as a novel and targetable vulnerability in drug-resistant NSCLC and highlight galangin as a promising sensitizer for overcoming resistance to two major targeted therapies.

Improvement from ECOG PS 2 to ECOG PS 0 to 1 was observed by the end of first cycle of treatment (57.9%). Safety and efficacy outcomes of sotorasib in this study were not affected with ECOG PS 2 and the history of CNS metastases and were consistent with those reported in key clinical trials.

Understanding these dynamics is essential for developing targeted public health strategies that address the unique challenges faced by this population, balancing their cultural heritage with the realities of modern American life. Further analysis and wider scope studies are necessary to explore the implications of these findings on health outcomes.

Lastly, in in-vivo studies, we observed no significant changes in tumor growth, and morphology between engineered organoids and their parental lines. In conclusion, our findings suggest that GFP- and RFP-expressing organoids retain the key characteristics of their parental lines and can serve as robust tools for both in-vitro and in-vivo drug screening studies.

However, pioneering work by Shokat and colleagues has led to the discovery of KRAS G12C-GDP mutant specific inhibitors, with two such inhibitors adagrasib and sotorasib now FDA approved for treatment of non-small cell lung cancer (NSCLC). Recent studies support the view that integration of AI algorithms with experimental methods is a key aspect in stream-lining the drug discovery process and identifying molecules with greater structural diversity, less off target effects than traditional screening methods. Furthermore, the authors believe that AI will eventually become standardized in drug discovery and existing pipelines specific to KRAS mutant inhibitor design will be expanded for additional KRAS mutations as well as other aggressive driver oncogenes across multiple cancers.

16k also demonstrated favorable drug-like properties, including good hepatic microsomal metabolic stability and a safer toxicity profile in vivo. In conclusion, this work expands the structural diversity of KRAS G12D inhibitors and highlights 16k as a promising lead compound for the development of targeted therapies against G12D-mutant cancers.

Blockade of CD9 restored extracellular tDNA and DNA sensing, reprogrammed TAMs, and synergized with PD-1 blockade in KRAS-mutant cancer models. These findings delineate a KRAS-CD9-FXR1 pathway that couples membrane mechanics to extracellular DNA clearance and immune evasion, providing a strong rationale for targeting CD9 to augment the efficacy of immune checkpoint blockade therapy.