Stem cells and lung cancer

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 bronchopulmonary 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. © Springer Science+Business Media, LLC 2009. All rights reserved.