The role of the tumor microenvironment in hematological malignancies and implication for therapy.
The tumor microenvironment is essential for tumor cell proliferation, angiogenesis, invasion, and metastasis by providing survival signals and a sanctuary site for tumor cells, by secretion of growth factors, pro-angiogenesis factors and direct adhesion molecule interactions. Our knowledge of microenvironment is only now beginning to unfold. In this review, the morphological and molecular characteristics of microenvironment in various hematological malignancies including acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, lymphoma, chronic lymphocytic leukemia, and multiple myeloma are summarized and the molecular mechanisms of microenvironment contributing to leukemogenesis are elucidated. We also aim to discuss the encouraging preclinical and clinical trials for treatment of hematological malignancies by targeting the tumor microenvironment. Further understanding of the signal transduction pathways between tumor cells and microenvironment will lead to the development of novel targeted therapeutic agents and more effective combination of current drugs for fighting hematological malignancies.
Zhou
Jianbiao
J
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Mauerer
Katja
K
Farina
Lucia
L
Gribben
John G
JG
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003510:Cyclohexanes; D016207:Cytokines / Q000627:therapeutic use; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D019337:Hematologic Neoplasms / Q000503:physiopathology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D016207:Cytokines; D061965:Matrix Metalloproteinase Inhibitors; D012717:Sesquiterpenes; D013186:Farnesyl-Diphosphate Farnesyltransferase; D000077609:O-(Chloroacetylcarbamoyl)fumagillol