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Grippo PJ, Munshi HG, editors. Pancreatic Cancer and Tumor Microenvironment. Trivandrum (India): Transworld Research Network; 2012.

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Pancreatic Cancer and Tumor Microenvironment.

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It takes two to tango : Pancreatic cancer and its microenvironment

, MBBS., MMedSci., PhD., AGAF.

Professor of Medicine, Director, Director, Pancreatic Research Group, South Western Sydney Clinical School, University of New South Wales, Sydney, NSW 2052, Australia

Pancreatic cancer is a devastating disease with a dismal prognosis, largely due to its propensity for early local and distant spread. Understandably, researchers in the field initially concentrated on trying to elucidate the biology of cancer cells themselves. It was a reasonable approach to think that unraveling the cellular and molecular processes in the cancer cells would point towards possible ways of destroying such malignant cells. However, despite significant advances in our knowledge regarding the molecular biology of pancreatic cancer cells, the success of treatment options was disappointing, with little improvement in the outlook for patients over the decades, even with combinations of therapies that included surgery, chemotherapy and radiotherapy.

While the research focus on cancer cell biology is not without merit, it has to be remembered that a tumor is much more than a clump of abnormal/malignant cells. It is a virtual ‘organ’ in itself since it contains not only cancer cells, but also has a blood and lymphatic supply, a neuronal network and infiltrating immune/inflammatory cells all embedded in a glycoprotein rich extracellular matrix. These structures form the ‘microenvironment’ of the tumor – it is an environment that most cancers cannot survive without since it provides nutrients, oxygen and a supportive milieu for abnormal growth.

In pancreatic cancer, pathologists and clinicians had long noted the prominent stromal/desmoplastic reaction which often appeared to ‘crowd out’ the cancer cells, so much so that some tumors appeared to be composed of 90% stroma and 10% tumor elements. However, up until 10 years ago, there was little research interest in the stroma surrounding pancreatic cancer cells, with the dense fibrosis often being dismissed as a mere epiphenomenon of the primary cancer. This situation changed drastically in the early 2000s, largely because of a significant breakthrough a few years earlier which provided unequivocal identification and characterization of the cell type that produces the fibrosis of both chronic pancreatitis and pancreatic cancer. These cells, known as the pancreatic stellate cells, have been intensely studied in recent years and evidence is accumulating of their central role in interactions with not only pancreatic cancer cells but also other cell types in the stromal reaction such as endothelial cells and immune cells. Even more interesting is the observation that PSCs from the primary tumor travel to distant metastatic sites, which has prompted a rethink of our understanding of tumor metastasis because it suggests that metastatic potential is not the sole preserve of cancer cells.

In view of the increased recognition of the key influence of tumorstromal interactions in local growth and distant spread of pancreatic cancer, the publication of this book is very timely. The Chapters have been written by senior investigators as well as up and coming researchers in the field who provide the readers with a state-of-the-art exposé on specific topics relevant to their experience and expertise. The Chapters describing the pathological characteristics (Chapter 1) as well as imaging findings (Chapter 2) of the desmoplastic reaction surrounding pancreatic cancer cells set the scene for subsequent Chapters that include a comprehensive discussion of current knowledge regarding the role of pancreatic stellate cells (Chapter 3) in the production of the stromal reaction and the critical place of these cells in stromal-tumor interactions facilitating cancer progression. A detailed discussion of animal models (Chapter 4), particularly mouse models that are the mainstays of in vivo research in this area, given the relative inaccessibility of the human pancreas during life, is highly useful in terms of underlining their importance in our current understanding of cancer development and progression. Chapters outlining epithelial-mesenchymal transition (Chapter 5), the role of the mesenchyme and the role of stem cells in progression and/or recurrence (Chapter 6) and the signaling pathways that mediate epithelial mesenchymal transition as well as other stromal-tumor interactions (Chapter 7), make an important contribution to the theme. This information prepares the ground for a discussion on the role of the tumor microenvironment in the well-known chemoresistance of pancreatic cancer (Chapter 8). Obviously, the ultimate goal of researchers in this field of tumor microenvironment interactions in pancreatic cancer is to be able to provide novel insights for improved approaches to pancreatic cancer treatment. The final Chapter discussing the development of potential strategies to target the stroma (Chapter 9) brings together the significant advances made by workers in recent years. There is no doubt that these novel approaches represent our best chance yet of winning the war against this deadly disease, which has claimed countless lives thus far.

Copyright © 2012, Transworld Research Network.
Bookshelf ID: NBK98928


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