LAUSR

Most human cancers display high levels of heterogeneity, a feature chemotherapy [6]. The study shows that NT5C1A is strongly expressed that often impacts negatively on the response to treatments. Indeed, while radio and/or chemotherapy initially cause remission of the tumor mass, residual neoplastic cells that are capable to withstand treatments can often give rise to tumor relapse, which typically presents with more aggressive and sometimes lethal phenotypes. In this regard, pancreatic ductal adenocarcinoma (PDAC) represents a remarkable example. PDAC is a devastating disease with a poor clinical outcome, which is mainly due to late diagnosis, resistance to chemotherapy and radiation and lack of specific targeted therapies [1,2]. As a consequence, most patients are diagnosed at an advanced stage and display an expected 5-year survival rate of ~5% [1,2]. Based on these features, PDAC is envisioned to represent the second cause of cancer-related death by 2020 [1,2]. These facts highlight the urgent need for identification of novel therapeutic targets and/or early biomarkers of the disease that may help significantly improve clinical management of the disease and life expectancy of patients. The poor sensitivity of PDAC cells to chemotherapy is related to many factors, including reduced bioavailability of the drugs in tumor cells, abnormalities in drugs metabolism and rapid acquisition of the capacity to activate alternative compensatory pathways [3]. Furthermore, the tumor microenvironment, including the surrounding stromal compartment and immune cells, contributes to the low response of PDAC cells to treatments and represents an additional problem in the design of novel therapies for this disease. The current standard adjuvant treatment in the advanced PDAC setting is still represented by gemcitabine used as single agent [4]. New therapeutic strategies are now available and include treatments with intensified regimens, such as the multidrug FOLFIRINOX or the combination of gemcitabine with nab-paclitaxel, alone or with further addition of cisplatin and capecitabine [5]. However, although these new regimens have lead to some small improvements in survival, life expectancy of advanced PDAC patients remains very poor [2]. In the present issue of Ebiomedicine, Patzak and colleagues examined the role of Cytosolic 5′-nucleotidase 1A (NT5C1A), a recently described gemcitabine-inactivating enzyme that dephosphorylate gemcitabine monophosphate (dFdCMP), in the response of PDAC cells to