KRAS G12D

Analysis of human LC samples revealed enrichment of pro-metastatic IL-10+ and VEGFA+ M2 macrophages, which correlated with poor clinical outcomes. Collectively, these findings demonstrate that NB-driven fructose metabolism induces epigenetic reprogramming of macrophages to promote LC progression and identify pro-metastatic M2 macrophages as potential prognostic biomarkers and therapeutic targets.

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.

In updated phase I clinical trial results, patients treated with zoldonrasib, a KRASG12D-selective inhibitor under study in non-small cell lung cancer, showed an objective response rate of 52%, a disease control rate of 93%, a median progression-free survival of 11.1 months, and a 73% overall survival at 12 months.

We evaluated KRAS G12D -specific (MRTX1133) and pan-KRAS inhibitor (RMC-6236) in KRAS mut organoid and orthotopic PDX models of AA. Additionally, KRAS inhibition remodels TME and may enhance innate immune signaling. These findings support continued clinical development of KRAS inhibitors in AA and provide a rationale for combination strategies targeting resistance pathways and stromal remodeling.

Although CSF1R inhibition alone was insufficient to improve tumor control, combinatorial blockade of PD-L1 and CD73 augmented systemic antitumor responses, and the addition of CSF1R inhibition in this context further enhanced both local and distant tumor control. These findings identify a CSF1-dependent myeloid resistance program that constrains ablation-induced systemic immunity and demonstrate that rational combination immunotherapy can potentiate the systemic efficacy of tumor ablation in PDAC.

P1, N=130, Not yet recruiting, Bayer

Single cell RNA sequencing indicated that loss of SCAP suppressed SREBP-dependent transcriptional programs in endocrine and exocrine precursors, but was associated with enhanced SREBP2 activity in fibroblastic populations, compatible with formation of a pro-tumorigenic tumor microenvironment. Together, these results implicate lipid metabolism via SCAP-SREBP signaling as an important metabolic regulator of acinar-ductal differentiation and pancreatic carcinogenesis.

Together, these articles reposition KRASG12R PDAC as a biologically constrained yet therapeutically exploitable subtype. See related article by Burge et al., p. 1854 See related article by Burge et al., p. 1868 See related article by Kamgar et al., p. 2042.

Tff2+ corpus progenitors represent a common cellular origin for SPEM and gastric dysplasia, challenge the conventional stepwise model of gastric carcinogenesis and indicate divergent differentiation programmes from Tff2+ progenitors.

P1, N=42, Recruiting, D3 Bio (Wuxi) Co., Ltd | Not yet recruiting --> Recruiting

P3, N=588, Recruiting, Incyte Corporation

In an HCT116 xenograft model, oral administration of SL43 (20 and 40 mg/kg) also significantly suppressed tumor growth (TGI = 57.2% and 74.9%, respectively), outperforming MRTX0902 (60 mg/kg, TGI = 47.1%) with no observable systemic toxicity. In conclusion, SL43 represents a potent and orally bioavailable SOS1 inhibitor that effectively suppresses KRAS signaling and exerts strong antitumor efficacy, highlighting its potential as a promising candidate for KRAS-mutant colorectal cancer.