The role of platelet growth factors in cancer therapy.
The use of myeloid growth factors has markedly reduced the complications of chemotherapy-induced neutropenia, however, abrogation of severe thrombocytopenia remains a major clinical problem. Platelet transfusions remain the standard method of preventing or treating thrombocytopenia but are associated with a variety of complications and are a limited resource. A number of cytokines have been clinically investigated for their thrombopoietic activity, the most promising of which is the recently cloned ligand to the hematopoietic growth factor receptor, c-Mpl. The c-Mpl ligand, also referred to as thrombopoietin, megakaryocyte growth and development factor (MGDF) and megapoietin, is a potent lineage-specific agent that promotes growth and maturation of megakaryocytes and their progenitors. It holds promise for clinical use in the treatment of iatrogenic or disease-associated bone marrow failure states and possibly in syndromes of excessive platelet consumption. Early clinical trials assessing the safety and activity of recombinant human MGDF are now underway.
Clarke
K
K
Center for Developmental Cancer Therapeutics, Parkville, Victoria, Australia.
Basser
R L
RL
D001792:Blood Platelets / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division; D019070:Cell Lineage; D002986:Clinical Trials as Topic; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000627:therapeutic use; D017370:Interleukin-11 / Q000627:therapeutic use; D015850:Interleukin-6 / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*
D006133:Growth Substances; D007375:Interleukin-1; D017370:Interleukin-11; D015850:Interleukin-6; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin