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.
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.
Together with the results of the AIO-PK-0104-trial, the present analysis supports the notion that KRAS mutation status is rather predictive than prognostic in advanced PC.
To identify genes that modulate sensitivity to MAPKi, we performed genome-scale CRISPR-Cas9 loss-of-function screens in two KRAS mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib.
At present, K-ras-2 mutation is not useful for differentiating pancreatic cancer from chronic pancreatitis or the identification of patients with chronic pancreatitis at risk for malignant transformation.
Despite the near universal occurrence of activating codon 12 KRAS somatic variants in pancreatic cancer, there is considerable heterogeneity in the molecular make-up, MAPK/ERK pathway activation states, and clinical outcome in this disease.
Efforts to model pancreatic cancer in mice have focused on mimicking genetic changes found in the human disease, particularly the activating KRAS mutations that occur in pancreatic tumors and their putative precursors, pancreatic intraepithelial neoplasia (PanIN).
K-ras gene mutations at codon 12 were detected in the sera of 14 of 20 patients with pancreatic carcinoma and in none of the six patients with chronic pancreatitis, or in the five healthy controls.
The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively.
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.
Remarkably, in 3D spheroid cancer cell cultures, some triple action compounds showed an antitumor potency up to 50-fold higher than cisplatin against a KRAS mutated pancreatic cancer cell line (PSN-1 cells).
The value of K-ras gene mutation for the detection of early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis remains uncertain in clinical practice.