Review article: manipulation of cell death--the development of novel strategies for the treatment of gastrointestinal disease

Abstract

The mechanisms underlying cell death are reviewed in order to propose new targets for the therapy of gastrointestinal disease. Necrosis is a set of precise biochemical and cellular lesions which culminate in cell destruction. A number of potential targets for drug therapy are discussed which will inhibit necrosis, including preservation of cellular ATP by inhibition of poly(ADP-ribose) polymerase. Such therapies may be useful either as adjuncts to other therapeutic modalities such as immunosuppressive agents for the treatment of inflammatory conditions or on their own for organ preservation prior to organ transplantation. Either excessive apoptosis or failure of apoptosis plays an important role in a variety of gastrointestinal diseases. Failure of apoptosis is of particular importance in the development of colorectal cancer. Mutations or deletions of p53, bcl-2 and myc prevents the appropriate deletion of malignant cells and causes resistance to anti-cancer drugs which act by the induction of apoptosis. Correction of these genetic defects or replacement of their function is a major strategy in cancer prevention and therapy. It is concluded that manipulation of cell death processes is an important new area for gastrointestinal research.