KRAS G12D

The study results identified ENPP1 as a contributor to pancreatitis-mediated pancreatic cancer and a potential therapeutic target for pancreatic carcinogenesis.

Our work defines the LY6D+ gastric-like cell state as a key driver linking early pre-malignant heterogeneity to PDAC initiation and progression. LY6D represents a pan-stage therapeutic target and a candidate biomarker for early detection and therapeutic targeting.

KRAS inhibitors, including KRAS G12D inhibitor MRTX1133, are promising therapeutics against KRAS-mutated pancreatic ductal adenocarcinoma (PDAC), but drug resistance limits their efficacy. Our study reveals that robust induction of apoptosis using a combination of BCL-xL PROTAC degrader and an mTOR inhibitor, significantly enhances MRTX1133 efficacy in PDAC models without increasing toxicity to normal tissues.

P1, N=25, Not yet recruiting, Sun Yat-sen University

Our study highlights the unique immunological and stromal features of AFL. Moreover, reinforcing their potential as precursor lesions, ADM and AFL exhibit variable alterations in the genes that have a critical role in PDAC carcinogenesis.

Importantly, CD38 inhibition improves the efficacy of low-dose anti-CTLA4 therapy. These findings uncover a previously uncharacterized cGAMP-STING-CD38 axis in macrophages supporting Treg survival and NSCLC progression and highlight potential therapeutic strategies for immune checkpoint blockade (ICB)-resistant cancers.

siG12D-LODER plus chemotherapy is safe, tolerable, and warrants further investigation in KRAS G12D/V-mutant LAPC.

The study highlights the heterogeneous prognostic impact of KRAS mutations in PDAC. These findings suggest that the prognostic relevance of KRAS mutations in PDAC may depend on clinical factors such as treatment modality and disease stage.

In murine models of MRTX1133-resistant PDAC, BET inhibition cooperated with MRTX1133 to markedly extend overall survival. As BET inhibitors are currently under clinical testing, the combination of MRTX1133 and BET inhibitors warrants further investigation, particularly in tumors that have developed resistance to KRAS inhibition.

Our findings demonstrate potential driver genes and mutational hotspots associated with CRC patient, characterizing the mutational landscape related to clinical characteristics. Significantly advancing our understanding of CRC's heterogeneous nature, this study lays a solid foundation for devising more efficacious management strategies.

KRAS mutations and hyperglycaemia drive O-GlcNAcylation of CLDN18.2 at its C-terminal T204 site. O-GlcNAcylated CLDN18.2 promotes poor prognosis and reduces the effectiveness of CLDN18.2-targeted therapies. Low dose MRTX1133 restores CLDN18.2 membrane localisation by reducing its O-GlcNAcylation and augments CLDN18.2-targeted therapy efficacy, offering a novel combinatorial strategy for KRAS-mutant PDAC.

PBRM1 maintains chromatin accessibility for hepatocyte differentiation-related genes. Its loss promotes differentiation toward cholangiocytes during injury or tumorigenesis, driving iCCA development.