Importantly, FGTI-2734 inhibited the growth of xenografts derived from four patients with pancreatic cancer with mutant KRAS (2G12D and 2 G12V) tumors.
These findings also showed that gene signatures related to KRAS dependency might be prospectively used to inform on decitabine sensitivity in a selected subset of patients with KRAS-mutated pancreatic cancer.
Western blot analysis revealed that LY-1816 markedly suppressed the Src signaling, and downregulated the expression of FOSL1; FOSL1 is an oncogene vulnerability in KRAS-driven pancreatic cancer.
Overexpression of DCLK1-AL Increases Tumor Cell Invasion, Drug Resistance, and KRAS Activation and Can Be Targeted to Inhibit Tumorigenesis in Pancreatic Cancer.
Initially demonstrated in oncogenic KRAS-driven models of pancreatic cancer, macropinocytosis triggers the internalization of extracellular proteins via discrete endocytic vesicles called macropinosomes.
Among the mutations of N-Ras, H-Ras, and K-Ras, the mutant K-Ras is the most prevalent target for the development of Lungs, colon, and pancreatic cancers.
Extensive analysis was performed in terms of cfDNA fragments to explore the reasons for higher detection rate of KRAS mutations in the circulation of pancreatic cancers.
Hyperinsulinemia is a risk factor for pancreatic cancer, but the function of insulin in carcinogenesis is unclear, so this study aimed to elucidate the carcinogenic effects of insulin and the synergistic effect with the KRAS mutation in the early stage of pancreatic cancer.
The receptor for advanced glycation end products (RAGE) has recently emerged as a chemotherapeutic target in KRAS driven pancreatic cancers both for treatment and in chemoprevention.
Our data suggest a crucial role of LIF in KRAS-driven pancreatic cancer and that blockade of LIF by neutralizing antibodies represents an attractive approach to improving therapeutic outcomes.
KRASG12D point mutation plays an important role in the incidence of non-small-cell lung cancer (NSCLC) as well as colorectal cancer, pancreatic cancer and breast cancer.
Our data indicates that targeting the MEK/ERK-FAM83A feed-forward loop opens up additional avenues for clinical therapy that bypass targeting of oncogenic KRAS in aggressive pancreatic cancers.
KRAS is the most commonly mutated oncogene in human cancer, with particularly high mutation frequencies in pancreatic cancers, colorectal cancers, and lung cancers [Ostrem, J. M., and Shokat, K. M. (2016) Nat.Rev.Drug Discovery 15, 771-785].
The aforementioned results indicate that KIS37 administration is a novel therapeutic strategy for targeting PDK4 in KRAS-activated intractable human pancreatic cancer.