McGowan Institute faculty member Eric Lagasse, Pharm.D., Ph.D., is an associate professor in the University of Pittsburgh Department of Pathology and the Director of the Cancer Stem Cell Center (a collaborative partnership of the McGowan Institute/University of Pittsburgh Cancer Institute). Recently, his paper, “Cancer stem cells with genetic instability: The best vehicle with the best engine for cancer,” made the top ten chart of articles that have been downloaded most frequently from the Gene Therapy website in recent weeks.
Gene Therapy covers both the research and clinical applications of the new genetic therapy techniques currently being developed. The application of molecular biology has revolutionized the understanding of many diseases and has been readily applied for diagnostic purposes. Over the last decade, gene therapy protocols have entered clinical trials in increasing numbers. Covering a wide spectrum of diseases, these studies promise to unite the diverse organ-based specialties into which modern medicine has become divided. Gene Therapy covers all aspects of gene therapy as applied to human disease, including preclinical animal experiments, novel platform technologies for gene transfer, and gene expression analysis. There are over 80,000 recipients who receive via e-mail a copy of the table of contents for the Gene Therapy issue in which an author’s article is published. There is an average of 145,000 page views across the Gene Therapy web site per month.
Dr. Lagasse’s Top 10 Paper abstract is here:
Our understanding of the role of stem cells in cancer development is evolving quickly. In the course of tumor expansion, a subpopulation of tumor cells with stem cell-like features has been noted. These cancer stem cells give rise to transit amplifying tumor cells, which comprise the majority of the tumor mass prior to terminal differentiation. Combining this finding with genetic instability, a well-known engine for cancer development and metastases, a new model emerges for cancer where normal stem cells and their cellular pathway acquire stochastic malignant abilities. In this model, when cancer stem cells self-renew, many genetic variants are produced. Just as microbes 'learn' to defeat antibiotics, genetically heterogeneous cancer stem cells may possibly acquire resistance to various chemotherapeutic approaches. Drug-resistant microorganisms selected by spontaneous mutation of bacterial DNA may not be so different than the drug-resistant and genetically instable cancer stem cells recurring after chemotherapeutic treatment. In this gloomy view of cancer, cancer stem cells with genetic instability can be considered as 'the best vehicle with the best engine', a formidable challenge for the future development of new anticancer therapies.
Illustration: McGowan Institute for Regenerative Medicine.
Abstract (Gene Therapy (2008) 15, 136–142)