Oxidative stress by targeted agents promotes cytotoxicity in hematologic malignancies.
The past decade has seen an exponential increase in the number of cancer therapies with defined molecular targets. Interestingly, many of these new agents are also documented to raise levels of intracellular reactive oxygen species (ROS) in addition to inhibiting a biochemical target. In most cases, the exact link between the primary target of the drug and effects on cellular redox status is unknown. However, it is important to understand the role of oxidative stress in promoting cytotoxicity by these agents, because the design of multiregimen strategies could conceivably build on these redox alterations. Also, drug resistance mediated by antioxidant defenses could potentially be anticipated and circumvented with improved knowledge of the redox-related effects of these targeted agents. Given the large number of targeted chemotherapies, in this review, we focus on selected agents that have shown promise in hematologic malignancies: proteasome inhibitors, histone deacetylase inhibitors, Bcl-2-targeted agents, and a kinase inhibitor called adaphostin. Despite structural differences within classes of these compounds, a commonality of causing increased oxidative stress exists, which contributes to induction of cell death.
Chandra
Joya
J
Department of Pediatrics Research, Unit 853, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. jchandra@mdanderson.org
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D020013:Calcium Signaling; D044127:Epigenesis, Genetic; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D006873:Hydroquinones; C404397:NSC 680410; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D000218:Adamantane