Our results revealed that KRAS mutations are correlated with an inflammatory tumor microenvironment and tumor immunogenicity, resulting in superior patient response to PD-1/PD-L1 inhibitors.
Patients with tumours harbouring mutation of TP53 and either KRAS or NRAS (32%) had a worse 5-year PFS than those with TP53/KRAS/NRAS wild-type tumours (54% vs. 72%, HR 1.75, p = 0.02).
While CDK4/6 represents a downstream target of both KRAS mutation and loss of the CDKN2A tumor suppressor in PDAC, clinical and preclinical studies indicate that pharmacological CDK4/6 inhibitors are only modestly effective.
Our results indicate that some of the minor KRAS mutations cause varying tumor formation activity and are important targets for developing anti-RAS agents as chemotherapeutic agents.
In all components (bilateral serous borderline tumors, low-grade serous carcinoma and mesonephric-like adenocarcinoma), an identical KRAS mutation was detected (NM_004985.4): c.35G>A, p.(G12D) proving a clonal association between the serous and mesonephric-like components and excluding a collision neoplasm.
Using laser-capture microdissection and droplet digital PCR, we investigated whether endosalpingiosis harbours the driver mutations in BRAF and KRAS that characterise ovarian low-grade serous neoplasms.
More than 1000 μm submucosal invasion and lymphovascular invasions were recognized only in group C. Mutation analyses identified KRAS mutation in one group C tumor as well as GNAS mutation in in one group A and group B tumors.
ERBB2 and KRAS inhibition cooperates to suppress PDAC cell growth in vitro and to promote tumor regression in nude mice, providing a rationale for testing an anti-ERBB2 drug in combination with a KRAS inhibitor in ERBB2-mutant PDAC patients that are currently untreatable.
This work shows that ERK inhibitors are effective in LKB1 and LKB1/KRAS mutated tumors, thus offering a therapeutic strategy for this prognostically unfavorable subgroup of patients.
The expression levels of miR31, miR92a, KRAS oncogene, and the c-MYC transcription factor were subexpressed upon 72 h post-treatment with kaempferol-3-<i>O</i>-glycoside compared with the control without treatment (<i>P</i> < .05); in contrast, the tumor suppressor genes AMPK (∼4.85, <i>P</i> = .005) and APC (∼2.71, <i>P</i> = .066) tumor suppressors genes were overexpressed.
The application of the approach was tested for detecting the KRAS codon 12/13 mutation in paired tumor and blood plasma samples from 20 colorectal cancer patients.
Patients with variants outside these criteria had FAP-related extracolonic manifestations, colorectal cancer aged <40, somatic KRAS c.34G > T variant in the tumor or a first-degree relative with >10 adenomas.
The results showed that the AZ628 and BP-1-102 combination showed strongly synergistic effects on KRAS(G12D) H838, KRAS(G12S) H292 and KRAS(G12V) H441 cells and significantly enhanced the inhibition of cell proliferation <i>in vitro</i> and tumor growth <i>in vivo</i> by promoting apoptosis compared with one inhibitor alone.
A total of 248 formalin-fixed paraffin-embedded (FFPE) tissue samples, with CRC tumors comprising more than 10% of the whole tissue sample, were included in the study and analyzed for specific KRAS mutations in codons 12 and 13.
We evaluated the effect of regorafenib based on KRAS mutation status and the sidedness of the primary tumor in patients with metastatic colorectal cancer (mCRC).
EGFR (28%), KRAS (22%), and MET (16%) are the most commonly mutated oncogenes, while the top mutated tumor suppressor genes are TP53 (69%) and RB1 (25%).
K-RAS mutant CRC cells (HCT116 and SW480), wild-type CRC cells (HT29), and HCT116 xenograft tumors were separated into the following six study groups: (1) untreated (control); (2) RT alone; (3) BEZ235 alone; (4) RT + BEZ235; (5) maintenance BEZ235 following RT + BEZ235 (RT + BEZ235 + mBEZ235); and (6) maintenance BEZ235 following BEZ235 (BEZ235 + mBEZ235).
Tumors with a mutated KRAS had an increased value at the 25th percentile of maximal standardized uptake value (SUV<sub>max</sub>) within their metabolic tumor volume (MTV) (P < .0001; odds ratio [OR] 1.99; 95 % confidence interval [CI] 1.37-2.90) and their contrast from the gray-level cooccurrence matrix (P = .005; OR 1.52; 95 % CI 1.14-2.04).