Novel anti-cancer agents in development: exciting prospects and new challenges.
A large number of cancer chemotherapeutic agents, are in development, many already undergoing clinical testing. A number of these compounds were designed either to modulate or inhibit molecular targets which have been identified as being critical to the development or control of cancer. Targets for inhibition include matrix metalloproteinases, mediators of signal transduction (tyrosine kinases, cyclin dependent kinases and other kinases such as protein kinase C and A) as well as ras expression and prenylation. Classes of potential inhibitory compounds include small molecules, humanized monoclonal antibodies or antisense oligonucleotides. Many of these compounds are relatively well advanced in development. Proof of principle has already been demonstrated in some instances and at least one such compound has been approved for use. Although these new compounds offer exciting opportunities, many bring with them real challenges in terms of the selection of appropriate trial design and surrogate end-points.
Seymour
L
L
National Cancer Institute of Canada Clinical Trials Group, Queens University, 18 Barrie Street, Kingston, Ontario, K7L 3N6.
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D018844:Cyclin-Dependent Kinases; D020782:Matrix Metalloproteinases