Dear Colleagues,

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the Western world. The prognosis is poor, with 1- and 5-year survival rates of about 20% and 6%, respectively. Systemic chemotherapy administered either after tumor resection surgery or in patients with metastatic disease has been shown to prolong survival; however, surgery is the only curative treatment. About 20% of patients with pancreatic cancer can be operated on with curative intent, because most have locally advanced or metastatic pancreatic cancer at the time of diagnosis. Resistance to therapy resulting from the unique tumor environment of PDAC, consisting of desmoplastic stroma, immune suppressive cells, and activated fibroblasts, as well as a lack of biomarkers, remains a clinical challenge, one that is unmet in terms of the development of novel therapeutic targets for an effective administration of the disease. In this Special Issue, we would like to solicit manuscripts covering the development of novel therapeutical drug targets and their associated mechanisms, which can provide a basis for exploring new targets and developing more advanced strategies.

Prof. Dr. Guishan Xiao
Dr. Bin Lu
Guest Editors

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• therapeutic targets
• pancreatic biology
• drug resistance
• tumor microenvironment
• cancer metabolism

Tentative outline:

Endoscopic Ultrasound Tissue Acquisition in the era of precision medicine for pancreatic cancer

Alberto Fantin, Martina Tessari, Ottavia De Simoni, Giulia Peserico, Monica Franco, Annalisa Masier, Sabina Grillo, Cingolani Linda, Chiara Cristofori, Tiziana Morbin, Attilio Pirillo, Mario Gruppo

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and it has been estimated that pancreatic cancer will surpass breast cancer as the third leading cause of cancer death by 2025. Regarding the diagnosis of pancreatic cancer, Endoscopic Ultrasound (EUS) is more sensitive, specific and accurate in the detection of pancreatic lesions than high-quality cross-sectional imaging, furthermore it provides the histopathological diagnosis performing EUS-guided tissue acquisition (EUS-TA). Unfortunately, the majority of PDAC patients are diagnosed at late tumor stages with locally advanced or metastatic  cancer and the overall survival at 5 years is about 5%. To improve survival in patients with PDAC, current research aims at identifying molecular targets and subgroups of PDAC that may benefit from personalized treatment, opening a new landscape for the so-called ‘precision oncology’ as well as finding biomarkers predicting a better treatment response. Recent insights from modern next-generation sequencing (NGS) technologies shed light on the biological rationale of the results achieved so far and showed the chance to improve the molecular characteristics of this cancer in order to better define a treatment.

The concept of precision medicine for PDAC has become popular in recent years and many work groups have made important efforts to describe its genetic and molecular alterations in order to stratify subclasses of patients with prognostic relevance and possible molecular based-treatment opportunity. Genomic profiling has revealed several actionable alterations and therapies targeting aberrations such as BRCA1/2 mutations, mismatch repair (MMR) deficiencies or NTRK1–3 fusions are now available in this subset of patients. The real-world implication of molecular classification remains to be established and numerous clinical trials are currenting under development to enforce precision medicine in clinical practice.

Other studies were able to create pancreatic cancer organoids that mimic the original characteristic of primitive neoplasm by means of EUS-TA to enable testing targeted drugs.

In this scenario,  thanks to the ability to obtain tissue samples with high adequacy, EUS-TA allows to deepen the knowledge of cancer by expanding the offer of effective drugs against it.