Medicine Matters oncology

Bortezomib (Velcade®) is a proteasome inhibitor that exerts its effects by increasing the availability of antitumor proteins. In CTCL, it has been suggested that constitutive expression of the NF-κB pathway plays a key role in CTCL pathogenesis and tumor-cell maintenance [20]. In vitro studies have shown that bortezomib treatment leads to downregulation of the NF-κB pathway, thereby promoting tumor cell apoptosis [21]. A trial of bortezomib in 10 patients with relapsed or refractory CTCL demonstrated durable responses in seven of these patients, suggesting that bortezomib has activity in CTCL [22]. Recently, the second generation proteasome inhibitor marizomib (MRZ; NPI-0052) has been found to have increased potency and duration of biological effects compared with bortezomib [23]. Thus, marizomib is now also under investigation for the treatment of refractory lymphoma.