KRAS G12D

P1, N=387, Recruiting, TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) | N=287 --> 387

Initial evaluations of C29h alone or together with the standard-of-care chemotherapeutic drug gemcitabine were conducted on NQO1high human and mouse PDAC cell lines and patient-derived organoids...Importantly, C29h treatment induced tumor regression and increased the survival of PDAC-bearing mice and optimal C29h-induced tumor regression was dependent on CD8+ T lymphocytes whose tumoral recruitment was enhanced by drug treatment. This study supports the use of C29h alone or as part of a drug combination as an effective and promising strategy for selective eradication of NRF2high PDAC.

Taken together, we demonstrate that Rad18 has context-specific tumor-suppressive activity. Given the prevalence of 4NQO-like environmental exposures, RAD18 is highly likely to shape human cancer genomes and perhaps influence other aspects of the tumorigenic process.

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