The proliferation rate paradox in antimitotic chemotherapy.
Cytotoxic cancer chemotherapy drugs are believed to gain selectivity by targeting cells that proliferate rapidly. However, the proliferation rate is low in many chemosensitive human cancers, and it is not clear how a drug that only kills dividing cells could promote tumor regression. Four potential solutions to this "proliferation rate paradox" are discussed for the microtubule-stabilizing drug paclitaxel: drug retention in tumors, killing of quiescent cells, targeting of noncancer cells in the tumor, and bystander effects. Testing these potential mechanisms of drug action will facilitate rational improvement of antimitotic chemotherapy and perhaps cytotoxic chemotherapy more generally.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. timothy_mitchison@hms.harvard.edu
Timothy J
TJ
Mitchison
D000818:Animals; D050256:Antimitotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024201:Bystander Effect; D002453:Cell Cycle; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
D050256:Antimitotic Agents