KRAS G12D

P1/2, N=49, Recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Our study demonstrates that ELK1 is a potential therapeutic target for AML, due to its critical role in regulating neutrophils differentiation.

In patients with non-small cell lung cancer (NSCLC), the objective response rate (ORR, unconfirmed) is 58.33%, and in patients with pancreatic ductal adenocarcinoma (PDAC) the ORR (unconfirmed) was 33.33% in the 1000-1200mg cohort. This study supports the clinical potential of RNK08954 in patients with KRAS G12D mutation either as a single agent or in combination.

Together, this study demonstrated that KRASG12R is capable of driving tumorigenesis despite the reduced ERK/MAPK nuclear translocation and transcriptional output. Although human KRASG12D and KRASG12R-mutant tumors display unexpected similarities in PI3K activity, the differential ERK/MAPK signaling activity and the extrinsic consequences on the TME provide support for using KRASG12R mutation status as a prognostic biomarker for therapeutic strategies.

While KRAS was historically considered undruggable, mutant-specific inhibitors, including non-covalent KRAS G12D inhibitor MRTX1133, have emerged...Efficacy in patient-derived organoids was comparable. This study demonstrates the potential of this nanomedicine platform for targeted delivery of KRAS mutant-specific inhibitors to human tumors.

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.