Haematologica Reports 2005; 1(issue 8):
68-69[prev][index][next]
Beyond bortezomib alone: combination therapy and new
strategies in targeting the proteasome
Richardson PG
Paul G. Richardson, MD Clinical Director The Jerome Lipper Multiple
Myeloma Center Dana Farber Cancer Institute Harvard Medical School
Boston, MA, USA
Bortezomib is a selective proteasome inhibitor that has
exhibited anti-proliferative, pro-apoptotic, and anti-angiogenic
properties in myeloma models.1-4 These effects result
from activation or inactivation of multiple signaling pathways. In
multiple myeloma (MM) cell lines, bortezomib induced downregulation
of growth and survival signals as well as upregulation of apoptotic
pathways, including mitochondrial release of cytochrome c and
activation of JNK, caspase-3 and -8.3 Bortezomib also inhibited
activation of nuclear factor-kappaB, through stabilization of
inhibitor-kappaB, resulting in decreased interleukin-6 secretion,
apoptosis, and chemosensitization of MM cells.1-4
Importantly, MM cells were 170 times more sensitive than normal
cells to bortezomib-induced apoptosis.1 [>Read full article in PDF]
