DNA-interactive agents.
Currently, approximately 40 drugs are registered for the chemotherapeutic treatment of cancer, the vast majority of which either interact directly with DNA (eg, alkylating, methylating, platinating agents, topoisomerase inhibitors), or affect DNA synthesis (antimetabolites). Whilst such agents remain of great importance in combination chemotherapy regimens, many cancer drug discovery groups have questioned whether any further significant gains may be made through the development of novel DNA-interactive drugs. Such agents tend to be associated with dose-limiting antiproliferative tissue toxicities (eg, myelo-suppression, nausea and vomiting, diarrhea or mucositis) which is indicative of their general lack of selectivity in targeting tumor versus normal tissue DNA. Perhaps surprisingly to some, Dr D Von Hoff (University of Texas Health Science Center, San Antonio, Texas, USA) proposed that the investigation of DNA-interactive agents is still yielding some promising agents. He illustrated this with the following new agents.
Kelland
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CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK. lloyd@icr.ac.uk