title: Pancreatic cancer stroma: understanding biology leads to new therapeutic strategies.
abstract: Pancreatic ductal adenocarcinoma (PDA) is among the deadliest cancers in the United States and in the world. Late diagnosis, early metastasis and lack of effective therapy are among the reasons why only 6% of patients diagnosed with PDA survive past 5 years. Despite development of targeted therapy against other cancers, little progression has been made in the treatment of PDA. Therefore, there is an urgent need for the development of new treatments. However, in order to proceed with treatments, the complicated biology of PDA needs to be understood first. Interestingly, majority of the tumor volume is not made of malignant epithelial cells but of stroma. In recent years, it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells, leading to cancer progression. The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery. Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery. In this review, we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.
authors.affiliation: Agnieszka Anna Rucki, Lei Zheng, Department of Oncology, The Sidney Kimmel Cancer Center, the Skip Viragh Clinical Pancreatic Cancer Center, and the Sol Goldman Pancreatic Cancer Center, Johns Hopkins University, Baltimore, MD 21287, United States.
authors.forename: Agnieszka Anna
authors.initials: AA
authors.lastname: Rucki
authors.affiliation: Agnieszka Anna Rucki, Lei Zheng, Department of Oncology, The Sidney Kimmel Cancer Center, the Skip Viragh Clinical Pancreatic Cancer Center, and the Sol Goldman Pancreatic Cancer Center, Johns Hopkins University, Baltimore, MD 21287, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer associated fibroblast; Fibroblast activation protein; Hepatic growth factor; Pancreatic ductal adenocarcinoma; Pancreatic stellate cells; Sonic hedgehog; Stroma; Tumor microenvironment