Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection

Table 4 Selected highlights

Selected recent advances	Genetic risk factors
	In 2009, the use of gene sequencing identified PALB2, which had previously been implicated in breast cancer, as a susceptibility gene for PDAC[28]
	Expression of the palladin gene has been shown to be upregulated by cohabitance of normal fibroblasts with epithelial cells expressing the K-Ras oncogene. In 2012, it was shown that the palladin gene, which codes for a cytoskeletal protein, promotes mechanisms for metastasis and outgrowth of tumerogenic cells[90]
	Also in 2012, gene sequencing indicated that ATM mutations result in a predisposition to PDAC; LOH was demonstrated in 2 kindreds with PDAC[77]
	Therapy
	For patients with diabetes, treatment with metformin is associated with a lower relative risk of pancreatic cancer[127,136,137]
	A 2011 case report detailing a complete pathological response of a BRCA2-associated pancreatic tumor to gemcitabine plus iniparib showed the potential for PARP inhibitors in the treatment of BRCA2-associated pancreatic cancer[41]. Similar clinical trials are currently underway
Screening	Screening goals
	The goal of PDAC screening is the detection and treatment of (1) resectable PDAC; (2) PanIN-3 lesions; and (3) IPMN with high-grade dysplasia
	Low prevalence and high risk cohort enrichment
	The low absolute risk of PDAC development precludes population-wide screening from a cost-benefit and absolute harm perspective. The opportunity to screen high-risk cohorts will vastly increase the PPV of a screening test
	Screening efforts
	Past screening efforts, using patients cohorts at a high risk of developing PDAC, have demonstrated diagnostic yields from 1.1% to 50%, depending on their definition of yield (Table 3). Current screening modalities may be costly and invasive, and therefore associated with some patient risk. Furthermore, the long-term implications for detection of small and clinically insignificant lesions are uncertain. Further studies are needed to determine appropriate surveillance
Anticipated future advances and screening possibilities	Risk stratification
	Personal, family, genetic and environmental history will allow risk stratification and development of tailored screening and surveillance programs
	Biomarkers
	Ongoing research that suggests a future for gene expression profiling, proteomics, metabolomics, and microRNA as diagnostic PDAC biomarkers
	Targeted therapy
	As with BRCA2-associated tumors and PARP inhibitors, tumor biology will increasingly dictate the subsequent therapy

PDAC: Pancreatic ductal adenocarcinomas; IPMN: Intraductal mucinous cystic neoplasm.