Failing to live up to the fanfare? A personal perspective on obstacles to the clinical development of thrombopoietic agents.
A number of hematopoietic growth factors have been identified that are active on megakaryocytes and platelets, but only 2, interleukin-11 (IL-11) and thrombopoietin, are being actively pursued clinically, with IL-11 approved for treatment of thrombocytopenia. The development of these agents in general has been disappointing, and in part this reflects the inherent biology of these factors with a failure to match clinical need with physiological function. The delayed action of these factors is also a consequence of the intrinsic biology of megakaryocytes and platelets, and thus is likely to be limiting regardless of which factor is employed. In addition, the development of these agents has occurred at a time when there is something of a decreasing demand for platelets, at least in the context of chemotherapy-induced thrombocytopenia. This decrease is the result of increased use of blood stem cells to support intensive chemotherapy procedures, reduced thresholds for platelet transfusion, and a decreasing role for intensive chemotherapy. These issues are discussed.
Basser
R L
RL
The Centre for Developmental Cancer Therapeutics, Parkville, Victoria, Australia.
Begley
C G
CG
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D013926:Thrombopoietin / Q000494:pharmacology / Q000502:physiology
D006133:Growth Substances; D013926:Thrombopoietin