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PMID: 18843284 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Bone marrow microenvironment and the identification of new targets for myeloma therapy.

Leukemia ·Vol. 23 ·No. 1 ·2009-01-00 ·Pages 10-24

Podar K, Chauhan D, Anderson KC

Abstract

The development of multiple myeloma (MM) is a complex multi-step process involving both early and late genetic changes in the tumor cell as well as selective supportive conditions by the bone marrow (BM) microenvironment. Indeed, it is now well established that MM cell-induced disruption of the BM homeostasis between the highly organized cellular and extracellular compartments supports MM cell proliferation, survival, migration and drug resistance through activation of various signaling (for example, PI3K/Akt, JAK/Stat-, Raf/MEK/MAPK-, NFkappaB- and Wnt-) pathways. Based on our enhanced understanding of the functional importance of the MM BM microenvironment and its inter-relation with the MM cell resulting in homing, seeding, proliferation and survival, new molecular targets have been identified and derived treatment regimens in MM have already changed fundamentally during recent years. These agents include thalidomide, its immunomodulatory derivative lenalidomide and the proteasome inhibitor bortezomib, which mediate tumor cytotoxicity in the BM milieu. Ongoing studies are further delineating MM pathogenesis in the BM to enhance cytotoxicity, avoid drug resistance and improve patient outcome.

MeSH Terms
Antineoplastic Agents/pharmacology,therapeutic use Bone Marrow/pathology Drug Delivery Systems/methods Humans Multiple Myeloma/drug therapy,pathology
Chemicals
Antineoplastic Agents
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Podar K
Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics, Dana Farber Cancer Institute, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, Boston, MA 02115, USA. [email protected]
Chauhan D
Anderson K C
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Article Info
Journal
Leukemia
Abbr.
Leukemia
ISSN
1476-5551
DOI
10.1038/leu.2008.259
Email
[email protected]
Published
2009-01-00
Epub
2008-00-09
Pages
10-24
Language
English
Region
England
NLM ID
8704895
PMCID
PMC3418600
Subset
IM
Grants
NCI NIH HHS · P50 CA100707-09 · United States
PHS HHS · P0-1 78378 · United States
NCI NIH HHS · R01 CA050947 · United States
NCI NIH HHS · R0-1 CA 50947 · United States
NCI NIH HHS · IP50CA100707 · United States
NCI NIH HHS · P50 CA100707 · United States
NCI NIH HHS · P50 CA100707-08 · United States
External Links
PubMed source DOI: 10.1038/leu.2008.259 PMC Full Text View journal details
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