A 68-year-old man with multiple myeloma on bortezomib therapy develops painful, burning paresthesias in his hands and feet. The pathophysiological mechanism of this drug-related complication involves:

• A Proteasome inhibition causing accumulation of misfolded proteins in Schwann cells
• B Direct mitochondrial toxicity and reactive oxygen species generation in dorsal root ganglia ✓
• C Inhibition of tubulin polymerization leading to axonal transport failure
• D Anti-myelin antibody formation via bortezomib-protein adducts

Explanation

Bortezomib-induced peripheral neuropathy primarily affects small sensory fibers and is attributed to direct mitochondrial toxicity and oxidative stress (reactive oxygen species generation) in dorsal root ganglion neurons, leading to neuronal apoptosis. Unlike vincristine, which inhibits tubulin polymerization, bortezomib's main neurotoxic mechanism involves mitochondrial dysfunction and endoplasmic reticulum stress in sensory neurons rather than Schwann cell proteasomal overload.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.