Friend or foe? The proteasome in combined cancer therapy.
The proteasome is a multicatalytic enzyme complex that is responsible for degradation of the vast majority of intracellular proteins. Thus, it is involved in diverse cellular processes such as proliferation, differentiation and apoptosis. Especially its latter function yielded in the development of specific proteasomal inhibitors which have recently entered clinical trials due to their tremendous apoptosis-inducing capability. However, several recent studies including ours provided substantial evidence that a combined treatment of tumors with apoptosis-inducing agents and proteasomal inhibitors might even cause adverse effects leading to a prolonged survival of tumor cells. Based on our model of a biphasic role for the proteasome in apoptosis, we believe that a successful combat of tumors that relies on a combinational therapy with proteasomal inhibitors requires careful evaluation of several critical aspects in order to avoid a friend becoming a foe.
Sohn
Dennis
D
University of Düsseldorf, Institute of Molecular Medicine, Universitätsstrasse 1, Düsseldorf, Germany.
Totzke
Gudrun
G
Schulze-Osthoff
Klaus
K
Jänicke
Reiner U
RU
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis; D002454:Cell Differentiation; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology*
D046988:Proteasome Endopeptidase Complex