<p>Is there a CDKN2A-centric network in pancreatic ductal adenocarcinoma?</p>

Abstract

Pancreatic cancer has a high mortality rate and its incidence has risen rapidly in recent years. Meanwhile, the diagnosis and treatment of this cancer remain challenging. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, but, currently, no sufficiently effective modalities for its treatment exist. The early diagnosis rate of pancreatic cancer is low and most patients have reached an advanced stage at the time of diagnosis. PDAC evolves from precancerous lesions and is highly aggressive and metastatic. It is essential to understand how the disease progresses and metastasizes. CDKN2A mutations are very common in PDAC. Therefore, here, we have performed a literature review and discuss the role of CDKN2A and some related genes in the development of PDAC, as well as the basis of gene targeting with a correlation coefficient of CDKN2A above 0.9 on the STRING website. It is noteworthy that the interaction of CDKN2A with each gene has been reported in the literature. The role of these genes and CDKN2A in PDAC may provide new directions that will advance the current knowledge base and treatment options since cancer progression is realized through interactions among cells. Our findings provide new insights into the treatment of PADC that can, to some extent, improve the diagnosis rate and quality of life of patients.

HNF1B inhibits cell proliferation via repression of SMAD6 expression in prostate cancer

“…CDK4 can inhibit the activity of CDKN2A, which is a transcription target of MYC 31 . Moreover, other researchers showed the relationship between CDKN2A and other five genes and built up a CDKN2A‐centric network regulation which might exist in pancreatic ductal adenocarcinoma (PDCA) 32 . HNF1B mutation might affect the interaction with CDKN2A, and this might depend on the location of the mutation.…”

Uncovering potential interventions for pancreatic cancer patients via mathematical modeling

“…PDAC has four common gene mutations: KRAS, TP53, SMAD4, and CDKN2A [13,24,25]. Notably, the HER2/neu oncogene mutation typically occurs in the precancerous stage, where HER2 binds to EGFR and activates its pathway.…”

Biological Hallmarks and New Therapeutic Approaches for the Treatment of PDAC

“…Previous studies have reported that CDKN2A is inactivated in about 95% of PDAC by different mechanisms such as homozygous deletion of both alleles, intragenic mutation in one allele or promoter hypermethylation. CDKN2A is inactivated in about 40% of cases by deletion of both alleles [ 41 , 42 , 43 , 44 ]; another 15% of PDAC shows hypermethylation of the promoter sequence for CDKN2A [ 41 , 45 , 46 , 47 ]. Moreover, further data confirmed the role of this mutation on the PDAC progression to a more aggressive phenotype.…”