Citation

O'Connell J. Expert Opinion on Therapeutic Targets 1999; 3(4): 601-611.

Copyright

(Copyright © 1999)

DOI

10.1517/14728222.3.4.601

PMID

unavailable

Abstract

Fas (CD95/APO-1) is a cell surface receptor which mediates a potent apoptotic death signal upon engagement by its ligand, FasL. Since tumour cells frequently co-express Fas and FasL, the prospect of therapeutically stimulating autocrine suicide of cancer cells via the Fas pathway is tantalising. To achieve this, mechanisms of acquired resistance to Fas-mediated apoptosis, inherent in cancers, must be overcome. Indeed, expression of FasL by Fas-resistant tumours appears to enhance malignancy by triggering apoptosis of Fas-sensitive antitumour immune effector cells. Therapeutic inhibition of this "Fas counterattack" against antitumour immune responses might improve immunotherapeutic approaches. Although restoring the Fas-sensitivity of tumours and inhibiting FasL-mediated counterattack against antitumour lymphocytes have been achieved experimentally in vitro, transferring such approaches to in vivo therapy represents an enormous challenge. © 1999 Ashley Publications Ltd.

Language: en

Keywords

antisense; apoptosis; cancer; chemoresistance; Fas (CD95/APO-1); Fas counterattack; Fas ligand (FasL); immunotherapy; metastasis; soluble FasL (sFasL)