In this study, we evaluated the cross-talk between CAF and TEC isolated from tumors generated in a mouse model of KRAS/mut p53-induced pancreatic cancer (KPC mice).
mutKRAS ctDNA was present in a majority of advanced PC patients (n = 36/54, 67%) and indicated tissue KRAS mutation status with a high sensitivity (75%) and specificity (100%).
KRAS, NRAS and BRAF mutations are among the most important oncogenic drivers in many major cancer types, such as melanoma, lung, colorectal and pancreatic cancer.
Despite research and drug development efforts focused on KRAS, no targeted therapy has been clinically approved for the treatment of pancreatic cancer with KRAS mutation.
Obese mice with KRAS (KC) mutation in the pancreas fed with high-fat calorie diet (HFCD) exhibit severe deficiencies in the NK cell expansion and function at the pre-neoplastic stage of pancreatic cancer.
K-Ras protein trafficking within the pancreatic cancer cells is effectively inhibited by the majority of statins; the inhibition is eliminated by isoprenoid intermediates of the mevalonate pathway.
In this study we examined the potential of three intrinsically fluorescent benzo[α]phenoxazines or BPZs (R=Cl, CH3, H) to induce cytotoxic autophagy in chemo and apoptosis-resistant, KRAS and p53 mutated pancreatic cancer model cell line, MIAPaCa-2.
Our work reveals galectin-3 as a druggable target for KRAS-addicted lung and pancreas cancers, and indicates integrin αvβ3 as a biomarker to identify susceptible tumors.<b>Significance:</b> There is a significant unmet need for therapies targeting <i>KRAS</i>-mutant cancers.
Furthermore, in silico transcriptome interrogation of The Cancer Genome Atlas (TCGA)-derived KRAS wild-type (n = 38) and mutant (n = 132) PC tumors revealed 391 differentially expressed genes.
In subgroup analyses, KRAS mutation in pancreatic cancer, colorectal cancer, non-small cell lung cancer and ovarian epithelial cancer had HRs of 2.81 (95% CI 1.83-4.30, P<0.01), 1.67 (95% CI 1.25-2.42, P<0.01), 1.64 (95% CI 1.13-2.39, P = 0.01) and 2.17 (95% 1.12-4.21, p = 0.02) for OS, respectively.