The emerging role of reactive oxygen species in cancer therapy.
The generation of reactive oxygen species (ROS) can be exploited therapeutically in the treatment of cancer. One of the first drugs to be developed that generates ROS was procarbazine. It is oxidised readily in an oxic environment to its azo derivative, generating ROS. Forty years ago, Berneis reported a synergistic effect in DNA degradation when procarbazine was combined with radiation; this was confirmed in preclinical in vivo modes. Early uncontrolled clinical trials suggested an enhancement of the radiation effect with procarbazine, but two randomised trials failed to confirm this. The role of ROS in cancer treatments and in the development of resistance to chemotherapy is now better understood. The possibility of exploiting ROS as a cancer treatment is re-emerging as a promising therapeutic option with the development of agents such as buthionine sulfoximine and motexafin gadolinium.
Renschler
Markus F
MF
Pharmacyclics, Inc., 995 East Arques Avenue, Sunnyvale, CA 94085-4521, USA. mrenschler@pcyc.com
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019328:Buthionine Sulfoximine / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004247:DNA / Q000378:metabolism; D006801:Humans; D008665:Metalloporphyrins / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D010084:Oxidation-Reduction; D011344:Procarbazine / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; D011344:Procarbazine; D019328:Buthionine Sulfoximine; C437683:motexafin gadolinium; D004247:DNA