TY - JOUR
T1 - Inhibitors of the cyclin-dependent kinase and PIM kinase pathways in the treatment of myeloma
AU - Ramakrishnan, Vijay G.
AU - Kumar, Shaji K.
N1 - Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Multiple myeloma (MM) cells are characterized by genomic alternations that lead to increased cell proliferation and resistance to therapeutic interventions. Up-regulation of cyclins is a characteristic finding in a significant proportion of myeloma patients, mediated through a variety of mechanisms including chromosomal translocations. Cyclins and the cyclin-dependent kinases (CDKs) play a critical role in the cell proliferation seen in MM, especially in the high-risk disease. Given this, CDK inhibitors have been evaluated in this disease, and studies so far have led to a mixed picture. Recent studies with targeted CDK inhibitors have shown early promise, and trials of these drugs in combination with other myeloma drugs are ongoing. The malignant plasma cells in MM are highly dependent on the microenvironment for their growth and survival. Multiple signaling pathways have been found to mediate the interactions between the microenvironment and the plasma cells, whether mediated through cytokines or adhesion molecules. The PIM kinase pathway appears to play a major role in the myeloma cell survival, and PIM kinase inhibitors have shown efficacy in the laboratory, and a recent clinical trial also demonstrates important clinical activity.
AB - Multiple myeloma (MM) cells are characterized by genomic alternations that lead to increased cell proliferation and resistance to therapeutic interventions. Up-regulation of cyclins is a characteristic finding in a significant proportion of myeloma patients, mediated through a variety of mechanisms including chromosomal translocations. Cyclins and the cyclin-dependent kinases (CDKs) play a critical role in the cell proliferation seen in MM, especially in the high-risk disease. Given this, CDK inhibitors have been evaluated in this disease, and studies so far have led to a mixed picture. Recent studies with targeted CDK inhibitors have shown early promise, and trials of these drugs in combination with other myeloma drugs are ongoing. The malignant plasma cells in MM are highly dependent on the microenvironment for their growth and survival. Multiple signaling pathways have been found to mediate the interactions between the microenvironment and the plasma cells, whether mediated through cytokines or adhesion molecules. The PIM kinase pathway appears to play a major role in the myeloma cell survival, and PIM kinase inhibitors have shown efficacy in the laboratory, and a recent clinical trial also demonstrates important clinical activity.
KW - CDK inhibitors
KW - PIM kinase inhibitors
KW - cell proliferation
KW - cyclin-dependent kinases (CDK)
KW - cyclins
KW - multiple myeloma (MM)
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U2 - 10.1097/PPO.0000000000000171
DO - 10.1097/PPO.0000000000000171
M3 - Review article
C2 - 26841010
AN - SCOPUS:84957671913
SN - 1528-9117
VL - 22
SP - 7
EP - 11
JO - Cancer Journal (United States)
JF - Cancer Journal (United States)
IS - 1
ER -