Trial Information

Is There a Role of Oxidative Stress in the Pathophysiology of Bortezomib Induced Peripheral Neuropathy (BIPN) in Multiple Myeloma Patients?

The proteasome inhibitor bortezomib has shown impressive clinical activity alone and in
combination with other novel agents for the treatment of multiple myeloma (MM).

Peripheral neuropathy is a significant dose limiting toxicity of bortezomib, which
typically occurs within the first treatment cycles with bortezomib, reaching plateau around
cycle 5, and does not appear to increase thereafter.

Although bortezomib is known to be selective proteasome inhibitor, the mechanisms of
cytotoxicity are poorly understood.

It has been theoretically hypothesized that bortezomib abrogates the degradation of I-kB,
which blocks the transcriptional activity of NF-kB, however, recent studies demonstrated
that bortezomib elicits activation of multiple pathways in cancer cells, such as reactive
oxygen species (ROS) pathway.

The involvement of oxidative stress is supported by emerging studies showing that ROS
generation plays a critical role in the initiation of the bortezomib induced apoptotic
cascade.

Oxidative stress is a complex and dynamic situation characterized by an imbalance between
the productions of ROS and the availability and action of antioxidants.