Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening

Abstract

Pancreatic cancer (PC) is a highly malignant and aggressive tumor. Despite medical advancement, the silent nature of PC results in only 20% of all cases considered resectable at the time of diagnosis. It is projected to become the second leading cause in 2030. Most pancreatic cancer cases are diagnosed in the advanced stages. Such cases are typically unresectable and are associated with a 5-year survival of less than 10%. Although there is no guideline consensus regarding recommendations for screening for pancreatic cancer, early detection has been associated with better outcomes. In addition to continued utilization of imaging and conventional tumor markers, clinicians should be aware of novel testing modalities that may be effective for early detection of pancreatic cancer in individuals with high-risk factors. The pathogenesis of PC is not well understood; however, various modifiable and non-modifiable factors have been implicated in pancreatic oncogenesis. PC detection in the earlier stages is associated with better outcomes; nevertheless, most oncological societies do not recommend universal screening as it may result in a high false-positive rate. Therefore, targeted screening for high-risk individuals represents a reasonable option. In this review, we aimed to summarize the pathogenesis, genetic risk factors, high-risk population, and screening modalities for PC.

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“…Currently, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, by 2030, it has been projected to be the second leading cause of cancer-related deaths in the USA (Badheeb et al 2022 ; Cai et al 2021 ). In China, both the incidence and mortality rates of pancreatic cancer have recently been on the rise (Chen et al 2016 ).…”

Recent Trends in Biosensing and Diagnostic Methods for Novel Cancer Biomarkers

“…In the recent decade, on a clinical level, CA 19-9 biomarker has become extremely useful for the diagnosis of pancreatic cancer. Normal human serum CA 19-9 levels can play an outstanding role in clinical diagnosis of urothelial and gastric cancers [ 122 , 123 ]. Consequently, there is a necessity to improve highly sensitive methods which can detect CA 19-9 values in patients with cancer.…”

Advances in the Early Diagnosis of Pancreatic Ductal Adenocarcinoma and Premalignant Pancreatic Lesions

“…While the modalities mentioned above are highly sensitive and specific for identifying lesions within the pancreas, a long-standing problem in the field is applying these imaging modalities to patients before their disease has become unresectable or metastatic. Although there are guidelines for identifying individuals who are at high risk of developing pancreatic cancer [ 25 ] based on risk factors including genetics/family history [ 26 , 27 ] and environmental/lifestyle factors [ 28 ], there are limitations to their utility [ 1 , 29 ]. The difficulties in identifying high-risk individuals are influenced by the biology of the disease, wherein >80% of pancreatic cancers have nonhereditary KRAS mutations; thus, most cases are the result of somatic mutations [ 30 ].…”

“…Pancreatic cancer is a relatively rare cancer. However, patients with pancreatic cancer are generally diagnosed with late-stage or metastatic disease, which limits their eligibility for surgery; moreover, systemic treatments do not dramatically extend overall survival in patients with late-stage pancreatic cancer [ 1 , 2 ]. Thus, while pancreatic cancer is only responsible for approximately 3% of all diagnosed malignancies, it accounts for approximately 10% of all cancer-related deaths.…”