Title:Pancreatic Cancer Metastasis: Are we being Pre-EMTed?
Volume: 21
Issue: 10
Author(s): Srustidhar Das and Surinder K. Batra
Affiliation:
Keywords:
Epithelial to mesenchymal transition (EMT), linear progression model, metastasis, pancreatic cancer, parallel progression model.
Abstract: Pancreatic cancer, often considered a metastatic disease at the time of clinical diagnosis due to lack of any reliable
early diagnostic marker(s), is refractory to conventional chemo- and radiotherapy and has a dismal 5-year survival
rate of only 6%. Although surgical removal of the primary tumor is considered to be curative, the 5-year survival rate is
no more than 20% even in patients with clear resection margins (R0). The recurrence of local and metastatic disease
(primarily liver metastasis) post resection is considered to be the leading cause of mortality in these patients. In addition,
instances of metastatic disease without any local recurrence post resection have also been observed. Cancer metastasis is
the primary cause of mortality in cancer patients and is classically viewed as a late event during the progression of the
disease, which is supported by the genetic studies used to understand the evolution of pancreatic cancer. However, this view has recently
been challenged by studies using mathematical modeling and genetically labeled mouse models of pancreatic cancer to understand the
dynamics of tumor cell dissemination and epithelial to mesenchymal transition (EMT) of tumor cells well before the primary tumor is
formed. Given that EMT is a hallmark process that initiates the metastatic seeding of cancer cells and the dismal prognosis of pancreatic
cancer patients even after efficient removal of the primary tumor (99.9%), an early dissemination hypothesis of cancer cells cannot be
undermined. In this review, we will discuss the current views regarding pancreatic cancer metastasis with particular emphasis on the
epithelial to mesenchymal transition, its influence on the selection of patients for surgical resection and the therapeutic intervention.
