Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities

Abstract

Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents such as bortezomib and lenalidomide have significantly improved overall survival, the disease is currently incurable with the emergence of drug resistance limiting the efficacy of chemotherapeutic strategies. Failure to cure the disease is in part due to the underlying genetic heterogeneity of the cancer. Myeloma progression is critically dependent on the surrounding microenvironment. Defining the interactions between myeloma cells and the more genetically stable hematopoietic and mesenchymal components of the bone microenvironment is critical for the development of new therapeutic targets. In this review, we discuss recent advances in our understanding of how microenvironmental elements contribute to myeloma progression and therapeutically, how those elements can or are currently being targeted in a bid to eradicate the disease.

Transmembrane Activator and CAML Interactor (TACI): Another Potential Target for Immunotherapy of Multiple Myeloma?

“…The BM microenvironment is known to be critical for the growth and survival of myeloma cells by protecting them from spontaneous and drug-induced apoptosis [6][7][8][9]. The interaction between myeloma and BM stromal cells is mainly mediated by soluble factors and adhesion molecules.…”

Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Therapies

“…Bone destruction is the hallmark of MM and is mediated by osteoblasts [35]. Osteoblasts are the most important components of the MM microenvironment.…”

Introductory Chapter: Multiple Myeloma in the Era of Novel Therapeutics

“…MM is a heterogeneous disease even in its etiology, and there are several risk factors for the disease that include old age; obesity; ionizing radiation; exposure to solvents and pesticides; agricultural occupations; autoimmune disorders such as pernicious anemia and ankylosing spondylitis; monoclonal gammopathy of undetermined significance; and familial predisposition [14][15][16][17][18]. One hallmark of MM is the presence of heterogeneous chromosomal aberrations and numerous genetic mutations that not only can help in risk stratifying the disease but also can affect management and prognosis to a large extent [7,8,19]. Recently, MM is stratified according to stage of the disease, plasma cell labeling index, cytogenetics, and gene expression profiling [20][21][22].…”