Biomedical Engineering Reference
In-Depth Information
Stem Cells and Lung Cancer
Adam Yagui-Beltra´ n, Biao He, and David M. Jablons
Abstract Lung cancer with its more than 1 million deaths per year is the leading
cause of cancer mortality for both men and women worldwide. Despite recent
advances in current treatment modalities, overall survival rates have hardly
improved. Overall 5-year lung cancer survival rate is approximately 15% in the
USA and these numbers are much lower in the developing world. The intrinsic
resistance shown by stem/progenitor cells following traditional chemotherapy
leads to disease recurrence and decreased patient survival and is a major clinical
challenge to overcome. Populations of cancer stem cells (CSCs) have been found
and characterized in multiple malignancies such as many hematological, breast,
colorectal, brain, pancreatic, and maxillofacial cancers; however, this has not
fully happened yet in human lung cancer, making such a task a paramount
necessity. In this chapter we explore the roles of the main developmental signaling
pathways in lung organogenesis and maintenance, together with the issue of
homeostatic pulmonary stem cells within specific 'niches' in the bronchopulmon-
ary tree. We explain how aberrations inflicted in many of the components of this
complex homeostatic machine can lead to the formation of lung cancer stem cells
with accumulated permanent mutations that allow them to repopulate their
tumors rendering these lesions resistant to traditional cytotoxic treatments,
resulting in dismal prognosis and poor survival rates. The aim, of course is to
ultimately integrate the knowledge of these mechanisms into tangible tools that
can be eventually translated into novel therapies for lung cancer.
Contents
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
194
2 Embryological Signaling Pathways in Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . .
195
2.1 The Wnt Signaling Pathway in Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . .
196
2.2 The Hedgehog Signaling Pathway in Lung Cancer . . . . . . . . . . . . . . . . . . . .
199
2.3 The Notch Signaling Pathway in Lung Cancer . . . . . . . . . . . . . . . . . . . . . . .
201
2.4 The Importance of Communication Between Developmental Pathways . . . .
202
D. M. Jablons (*)
Department of Surgery, University of California San Francisco Cancer Centre,
1600 Divisadero St., Box 1724, San Francisco, CA 94143-1724, USA
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