Circulating tumor cells in the diagnosis and management of pancreatic cancer

Abstract

Pancreatic cancers are typically resistant to chemo and radiation therapy and are predisposed to distant metastases. Circulating tumor cells (CTCs) are tumor cells disseminated from primary and metastatic sites and can be isolated from peripheral blood. CTC may overcome the limitation of the current available tumor markers, CA19-9. As a surrogate for 'real-time biopsy', CTCs allow recurrent assessment of a tumor's biological activity. We review the current methodologies for CTC extraction and characterization including antibody-based immunological assays, PCR-based assays, and novel technologies based on the physical or biological characteristics of CTCs. CTCs also provide an accessible link to the existence of epithelial to mesenchymal transition, tumor stem cell markers, and ongoing clonal mutations and epigenetic changes in the tumor. We also explore the potential of using CTC profiling in diagnosis, selection of neoadjuvant and adjuvant therapy, detection of recurrent disease, examination of pharmacodynamic biomarkers, as well as in gene therapy and immunotherapy for pancreatic cancer. Ongoing CTC characterization not only has the potential to represent all cells shed from primary pancreatic tumor and each metastatic site, but also allows dynamic sampling at multiple time points during the clinical course to identify the subpopulations of CTCs and the specific molecules driving metastasis and chemo resistance. We predict that CTC genotyping and phenotyping will play an increasing role in personalized therapy and in identification of novel therapeutic targets as well as monitoring the course and status of the disease.

Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interest.

Copyright © 2012 Elsevier B.V. All rights reserved.

Figures

Figure 1

Two cancer stem cell pools were found within a primary tumor of pancreas: intrinsic cancer stem cells, and induced cancer stem cells which had undergone epithelial mesenchymal transition (EMT) induced by transformation signals released from the microenvironment and from stroma cells. Circulating tumor cells (CTCs) comprise of cancer stem cells and differentiated tumor cells circulate through normal vessels and capillaries, and neovessles formed by tumor-induced angiogenesis, migrate to distant organs, extravasate, colonize and form distant metastasis clones. CTCs could also colonize their origin tumor in a process called ‘self-seeding’, and result in altering the tumors microenvironment, making it more supportive of tumor growth. CTCs profiling assays allow dynamic sampling during the clinical course to identify the subpopulations of CTCs and their specific molecules driving metastasis and chemoresistance for discovering novel targeted interventions.