Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at an advanced stage, resulting in poor prognosis. Traditional tissue biopsies remain the gold standard for making a diagnosis, but have an obvious disadvantage in their inapplicability for frequent sampling. Blood-based biopsies represent a non-invasive method which potentially offers easy and repeated sampling, leading to the early detection and real-time monitoring of the disease and hopefully an accurate prognosis. Given the urgent need for a reliable biomarker that can estimate a patient’s condition and response to an assigned treatment, blood-based biopsies are emerging as a potential new tool for improving patients’ survival and surveillance. In this article, we discuss the current advances and challenges in using liquid biopsies for pancreatic cancer, focusing on circulating tumour DNA (ctDNA), extracellular vesicles (EVs), and circulating tumour cells (CTCs), and compare the performance and reliability of different biomarkers and combinations of biomarkers.

Biliary tract cancers (BTCs) comprise a heterogeneous group of malignancies arising from the biliary tree, including cholangiocarcinomas and gallbladder carcinomas. Although their incidence is rising globally in Western countries, these cancers are rare and most often diagnosed at advanced stages. Their molecular heterogeneity and frequent resistance to therapy further contribute to their dismal prognosis. In recent years, molecular profiling studies have led to a better understanding of BTC biology and have opened new therapeutic opportunities, particularly for patients with advanced or metastatic disease. Alterations in DNA damage repair (DDR) genes have been identified in a substantial proportion of BTC cases, with some cohorts observing frequencies approaching ~70%. These genetic alterations play a critical role in tumorigenesis and disease progression and may contribute to treatment resistance. In this article, we discuss the current knowledge on: (1) the main DDR signaling pathways; (2) the prevalence of DDR gene alterations across BTC subtypes; (3) the potential of DDR gene alterations as prognostic and/or predictive biomarkers of treatment response; and (4) the latest advances in DDR-based targeted therapies and ongoing clinical trials in BTC.