Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic implications.
Multiple myeloma (MM), a hematologic malignancy, remains fatal despite all available therapies. Initial treatment with conventional drugs effectively induces MM cell death/apoptosis; however, prolonged drug exposures results in the development of de novo chemoresistance. Because MM is a bone marrow (BM) cancer, the progression of disease and drug efficacy is highly influenced by the BM microenvironment. Novel agents, such as proteasome inhibitors (PS-341), 2-methoxyestradiol (2ME2), thalidomide and its immunomodulatory derivatives (IMiDs), and histone deacetylase (HDAC) inhibitors target the MM cell in its BM microenvironment; thereby enhancing anti-MM activity as well as preventing development of drug-resistance. The transcriptional events and signaling pathways, which mediate these responses in MM cells are now being delineated, and may serve to identify novel therapeutic targets based upon interrupting MM cell growth or triggering MM cell death.
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The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. kenneth.anderson@dfci.harvard.edu
Anderson
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D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016923:Cell Death; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D048031:JNK Mitogen-Activated Protein Kinases; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases