2nd Gordon Hamilton Fairley lecture. Need for new approaches to the treatment of patients in clinical remission, with special reference to acute myeloid leukaemia.
A serious limitation of chemotherapy for acute myeloid leukaemia (AML), Hodgkins disease and some classes of breast cancer is that, even when clinically evident disease responds well, the same chemotherapy when given during remission does not affect the rate of relapse after chemotherapeutic or surgical ablation of the primary disease. This cannot, in general, be caused by genetic adaptation of the residual cancer cells which renders them resistant to specific drugs, because after relapse further remissions can be obtained with the same drugs that were ineffective by chronic administration in prolonging remission. The resistance of the residual cells may arise from mechanisms such as inaccessibility for anatomical or other reasons, or because of a change in metabolic state which causes these cells temporarily to cease division, when they cannot be harmed by cycle-dependent drugs and repair damage sustained from cycle-independent drugs. Limited differentiation has been shown capable of reversal and this may be a mechanism which leads to quiescence and associated "resistance", particularly in the case of AML. Where such resistance occurs treatment during remission-or as an adjuvant to surgery and radiotherapy-may have to rely on mechanisms which are independent of cellular proliferation such as processes associated with graft-versus-host-disease or the induction of terminal differentiation. A model for studying the nature of resistance of residual cancer and for testing treatments that might be active against cancer cells in this state may be dormant metastases. The latter are malignant cells which appear to be in peaceful co-existence with their host and which in experimental systems have been induced to grow into lethal metastases by perturbation of the host by surgical trauma, by hormonal manipulation or by immunosuppression.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D004351:Drug Resistance; D006689:Hodgkin Disease / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012008:Recurrence; D013997:Time Factors
D000970:Antineoplastic Agents