Modulation of the apoptotic response: Potential for improving the outcome in clinical radiotherapy Academic Article Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Sphingolipids

abstract

  • The most prevalent mechanism of cell kill by radiation is mitosis dependent and results from lethal DNA double-strand breaks and failure to maintain normal replication. Apoptosis is believed to represent a minor component of the clinical effects of radiation. Apoptosis is a preprogrammed death pathway that is constitutively expressed in many cells, albeit in an inactive form, regulated by antiapoptotic mechanisms. Data are presented to show that in irradiated cells the balance between proapoptotic and antiapoptotic signaling may determine the apoptotic outcome in vitro and in vivo. This balance can be modulated by pharmacological intervention to produce a more proapoptotic phenotype, increasing apoptotic cell kill by radiation. These studies establish the basic principles of signaling-based apoptosis therapy, designed to overcome the relative resistance to radiation-induced apoptosis and to improve the therapeutic ratio in the treatment of human tumors with fractionated radiation.

publication date

  • November 13, 1996

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S1053-4296(96)80023-3

PubMed ID

  • 10717185

Additional Document Info

start page

  • 273

end page

  • 283

volume

  • 6

number

  • 4