Minimizing drug resistance. The somatic mutation model and gestational trophoblastic neoplasia.
Because of its curability, gestational trophoblastic neoplasia provides a valuable framework within which models of tumor chemotherapy can be examined. The Goldie-Coldman hypothesis, one such model, holds that resistance to chemotherapeutic drugs can be acquired in human tumors as a result of spontaneous mutation. This paper examines in depth some implications of this hypothesis in gestational trophoblastic neoplasia. Several observed treatment phenomena in this disease are in accord with the predictions of the somatic mutation model, and the model may be used to guide future clinical investigation. In particular, there is a need to elaborate cross-resistance profiles between drugs commonly used to treat trophoblastic neoplasia. This information could be used to develop new combination chemotherapy regimens as well as strategies for alternating non-cross-resistant combination chemotherapy regimens.
Dembo
A J
AJ
University of Toronto, Princess Margaret Hospital, Ontario, Canada.
D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D011247:Pregnancy; D011336:Probability; D011379:Prognosis; D014328:Trophoblastic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents