Pancreatic Cancer—Challenges and Breakthroughs

Dear Colleagues, 

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of pancreatic cancers, and its mortality has been constantly increasing over the past 10 years. PDAC is a very aggressive tumor with a poor prognosis and inadequate response to treatment. Many factors contribute to this therapeutic failure, including lack of symptoms until the tumor reaches an advanced stage, leading to late diagnosis; very early local and lymphatic and hematic spread; advanced age of patients; important development of a pro-tumoral and hyperfibrotic stroma; high genetic and metabolic heterogeneity; poor vascular supply; a highly acidic matrix; extreme hypoxia; and early development of resistance to the available therapeutic options. Indeed, in most cases, the disease is silent for a long time, and when it does become symptomatic, it is too late for ablative surgery, which is one of the reasons behind the poor survival rates associated with the disease. Even when surgery is possible, relapses are frequent, and the causes of this devastating picture are the low efficacy of and early resistance to all known chemotherapeutic treatments. Despite extensive translational and clinical investigations over the last three decades, meaningful advances in PDAC therapeutics have not been realized. Unless solutions to chemoresistance and drug delivery to the cell are found, the situation will not change.

The lack of effective therapies has served as an impetus to further improve our understanding of pancreatic tumor biology to identify alternative treatment strategies. Significant research strides in recent years have contributed substantially to our understanding of PDAC. These studies have identified key driver mutations, signaling pathways, and tumor microenvironment interactions that promote disease progression, regulate metastasis, and drive therapeutic resistance.

PDAC treatment should be multidirectional since such an approach would reduce chemoresistance, and in this regard, novel therapeutic approaches are being actively investigated. The spectrum of future options is wide, and the research papers and reviews in this Special Issue will cover recent discoveries in PDAC biology, multiple causes of treatment resistance in PDAC, and possible resolutions to this impasse in the near and far future.

Dr. Stephan J. Reshkin
Dr. Rosa Angela Cardone
Guest Editors

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• pancreatic ductal adenocarcinoma
• resistance to treatment
• gemcitabine
• FOLFIRINOX
• nab-paclitaxel
• desmoplastic reaction
• acidic and/or hypoxic microenvironment
• novel targeted therapies
• adaptive plasticity