The tumor microenvironment as a determinant of cancer cell survival: a possible mechanism for de novo drug resistance.
The influence of the microenvironment in the pathogenesis and progression of human cancer has traditionally been considered in the context of solid tumors. More recently, evidence has been accumulating to support the role of the bone marrow microenvironment in hematologic malignancies as well, particularly in multiple myeloma. This review focuses on myeloma as a model to demonstrate that the bone marrow microenvironment provides a sanctuary against programmed cell death and promotes tumor cell survival and progression. Additionally, the protective effects of the bone marrow milieu may confer a protection from cytotoxic drugs, allowing the emergence of drug-resistant tumors. These advances may assist in the design of novel therapeutic approaches to enhance the efficacy of standard chemotherapeutic drugs.
Shain
K H
KH
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa 33612, USA.
Landowski
T H
TH
Dalton
W S
WS
D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D016923:Cell Death; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism
D016023:Integrins; D019014:fas Receptor