Molecular markers of pancreatic cancer: development and clinical relevance

Abstract

Many molecular markers have been proposed for the early diagnosis of PC, but most are not ready to be included as part of the routine diagnostic algorithm because they still lack sensitivity, specificity or reproducibility. CA 19-9 remains the most useful molecular marker for the diagnosis and follow-up of clinically and radiological evident pancreatic cancer.

A Novel Serum Metabolomics-Based Diagnostic Approach to Pancreatic Cancer

“…Screening tests for the general population have to be accurate, safe, and convenient, as well as capable of high throughput. Many researchers have devoted considerable effort to discovering biomarkers of pancreatic cancer (8)(9)(10), and CA242 (11), M2-pyruvate kinase (12), PBF-4 (13), MIC-1 (14), PNA-binding glycoprotein (15), hTert (16), MMP-2 (17), and synuclein-g (18) have been reported as candidate biomarkers, but they were not clinically superior to CA19-9 or other clinical examinations.…”

Disruption of Cell Cycle Machinery in Pancreatic Cancer

“…This suggests enhanced activity of cyclin D-CDK4/6 complexes makes an important contribution to development of pancreatic cancer, consistent with the common overexpression of cyclin D1 (Fry, et al, 2008). The mechanism of p16 loss is diverse, involving homozygous deletion (40%), intragenic mutation followed by inactivation of the second allele (40%), and methylation inactivation of the promoter (10-15%) (Gansauge, et al, 1997, Kornmann, Marko, et al, 1998a.…”

“…& Roberts, 1999, Wang, Q., et al, 2011a. In pancreatic cancer, cyclin D1 overexpression and p16 inactivation are very common events, emphasizing the importance of disrupting G1 progression to disease development (Chen, Jinyun, et al, 2009b, Fry, et al, 2008, Gansauge, et al, 1997, Kornmann, Marko, et al, 1998a, Schutte, et al, 1997. A major goal of E2F liberated by cyclin D-CDK4/6 is synthesizing cyclin E, which binds and activates CDK2 to continue progression through G1 and prepare for the S phase transition (Roberts & Sherr, 2003, Sheaff & Roberts, 1998.…”

“…A number of additional genetic disruptions appear to be required for mutant K-ras induced transformation. Of particular interest is excess cyclin D1, itself a downstream target of Ras that is commonly mutated in the disease state (Fry, et al, 2008, Gansauge, et al, 1997, Kornmann, Marko, et al, 1998a. Given the pleotropic effects of Ras signaling, further work is required to completely describe its contribution to transformation.…”

Point Mutations, Their Transition Rates and Involvements in Human and Animal Disorders

“…Mitochondria have further been implicated in the carcinogenic process because of their role in apoptosis and other aspects of tumour biology, alongside ROS generation (Jakupciak et al, 2005). In many types of human malignancy such as colorectal, liver, breast, pancreatic, lung, prostate, bladder and skin cancer somatic mtDNA mutations have been detected (Durham et al, 2003;Dasgupta et al, 2008;Fry et al, 2008;Yin et al, 2010;Choi et al, 2011;Namslauer et al, 2011;Potenza et al, 2011). Furthermore, sequence variations of mtDNA have been observed in preneoplastic lesions, which suggest generation of mutations early in tumour progression (Parr et al, 2006).…”