Liquid biopsy in Brazilian pancreatic cancer patients

Pancreatic cancer ranks 13th in incidence in Brazil and 6th in mortality among all tumors, accounting for 4% of cancer-related deaths in the country, with eleven thousand annual fatalities. Despite recent advances, the 5-year survival rate remains extremely low, at 10% even in developed countries. Furthermore, its incidence has almost doubled in the last two decades and is projected to become the second leading cause of cancer-related death in the USA by 2030. Non-hereditary risk factors are not yet fully understood, though associations have been described with smoking, diabetes, obesity, and chronic pancreatitis. Regarding somatic genetic alterations, four genes stand out with the highest mutation rates: KRAS, TP53, SMAD4, and CDKN2A. In addition to its high aggressiveness, another key factor contributing to the high rate and mortality of this disease is its difficult and late diagnosis. This diagnosis is aided by imaging exams such as magnetic resonance imaging (MRI) and computed tomography (CT), but confirmation occurs via biopsy or even surgically. Therefore, the development of sensitive and non-invasive diagnostic methods utilizing next-generation sequencing (NGS) in plasma is essential for scientific and clinical advancement. Consequently, diagnosis will be achieved earlier, enabling improved therapeutic and clinical management, and increasing the survival of pancreatic cancer patients. This project aims to develop an NGS-based molecular liquid biopsy test for the detection of mutations in KRAS, TP53, SMAD4, and CDKN2A genes in cell-free DNA from pancreatic cancer patients. Beyond its molecular diagnostic utility, this test can also be employed for disease prognosis assessment, by detecting the accumulation of mutations in these genes throughout the course of the disease. Thus, we will present a sensitive, modern, and clinically applicable solution for pancreatic cancer, which will represent a substantial advance in its diagnosis and prognosis.