Cancer stem cells and impaired apoptosis.
For more than 100 years scientists have fervently sought the fundamental origins of tumorigenesis, with the ultimate hope of discovering a cure. Indeed, these efforts have led to a significant understanding that multiple genetic and molecular aberrations, such as increased proliferation and the inhibition of apoptosis, contribute to the canonical characteristics of cancer. Despite these advances in our knowledge, a more thorough understanding, such as the precise cells, which are the targets of neoplastic transformation, especially in solid tumors, is currently lacking. An emerging hypothesis in the field is that cancer arises and is sustained from a rare subpopulation of tumor cells with characteristics that are highly similar to stem cells, such as the ability to self-renew and differentiate. In addition, more recent studies indicate that stem cell self-renewal pathways that are active primarily during embryonic development and adult tissue repair may be aberrantly activated in various cancers. This chapter introduces the cancer stem cell hypothesis; explores evidence for the presence of cancer stem cells, particularly in leukemia; and discusses various classical stem cell self-renewal pathways in relation to cancer. Investigating the role of cancer stem cells in the context of the major characteristics of cancer, especially impaired apoptosis, offers great promise for the design of superior tumor-selective and apoptosis-inducing therapies.
Jagani
Zainab
Z
Novartis Institutes for Biomedical Research, Novartis Oncology, 250 Massachussetts Avenue, Cambridge, MA 02139, USA. zainab.jagani@novartis.com
Khosravi-Far
Roya
R
D000818:Animals; D017209:Apoptosis; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*