Targeting apoptosis pathways in cancer stem cells

Michele Signore, Lucia Ricci-Vitiani, Ruggero De Maria Marchiano

Research output: Contribution to journalArticle

79 Citations (Scopus)


There is a significant void in cancer biology with regard to the elucidation of the mechanisms that underlie tumor formation and progression. Recently, the existence of a hierarchy within cancer cell populations has been demonstrated experimentally for several tumor types. The identification of a tumor cell subset that is capable of self-renewal and, concurrently, generation into more differentiated progeny has engendered new perspectives toward selective targeting of tumors. Although the identification of the so-called "cancer stem cells" (CSCs) is a leap in the study of cancer ontogenesis, therapeutic targeting of such cells is plagued by significant difficulties. CSCs are able to evade the control mechanisms that regulate cell survival and proliferation. Apoptosis is one of the most critical and well-studied mechanisms, governing tissue development and homeostasis through a complex network of molecules that mediate death and survival signals. Escape from such a finely tuned death program is a prerequisite for any tumor-initiating cell. Thus, many compounds have been developed to target cancer cells and induce apoptosis directly or indirectly. Several TRAIL receptor agonists are in Phase I or II trials, and IAP inhibitors are undergoing clinical examination to exploit their ability to enhance ionizing radiation- and chemotherapy-induced apoptosis. Further, the EGF-R/Akt pro-survival signaling axis is one of the most frequently explored sources of targets for indirect apoptosis induction, as evidenced by the significant amount of molecules designed to target this pathway and have been approved by the FDA or are under clinical evaluation. Despite the promise of these magic bullets, the absence of reliable clinical models has considerably diminished the therapeutic potential of targeted therapies considerably. A more systematic molecular characterization of the tumor-initiating cell population in many tumors will allow us to refine the stimuli that force CSCs to die, thus accelerating the development of more effective treatment for cancer. © 2011 Elsevier Ireland Ltd.
Original languageEnglish
Pages (from-to)374-382
Number of pages9
JournalCancer Letters
Publication statusPublished - 2013


  • Animals
  • Apoptosis
  • Cancer Research
  • Cancer stem cells
  • Clinical Trials as Topic
  • DNA Repair
  • Disease Progression
  • Drug Resistance, Multiple
  • Humans
  • Kinase inhibitors
  • Neoplasm Transplantation
  • Neoplasms
  • Neoplastic Stem Cells
  • Oncology
  • Protein Kinase Inhibitors
  • Signal Transduction
  • Signaling pathway


Dive into the research topics of 'Targeting apoptosis pathways in cancer stem cells'. Together they form a unique fingerprint.

Cite this