Bortezomib in Waldenstrom’s Macroglobulinemia
Waldenstrom’s macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by the presence of a lymphoplasmacytic infiltrate in the bone marrow and the presence of a serum monoclonal protein IgM. Despite the clinical efficacy of conventional therapies, most patients eventually relapse and the disease remains incurable. Therefore, novel therapeutic agents are needed for the treatment of WM. The multicatalytic ubiquitin–proteasome pathway plays an important role in the targeted degradation of a wide spectrum of proteins involved in the regulation of several cellular processes. The proteasome itself has been selected as a target for cancer therapy. Bortezomib represents the first proteasome inhibitor to enter clinical trials. The enthusiastic preclinical and clinical results exerted by bortezomib in multiple myeloma, as well as other hematological malignancies including WM, has validated the idea that the proteasome is an important target in cancer therapy.
KeywordsMultiple Myeloma Proteasome Inhibitor Bortezomib Treatment Lymphoplasmacytic Lymphoma Chick Embryo Chorioallantoic Membrane
- 1.Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al (2003) Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s macroglobulinemia. Semin Oncol 30:110–115PubMedCrossRefGoogle Scholar
- 10.Kyle RA, Treon SP, Alexanian R, Barlogie B, Bjorkholm M, Dhodapkar M et al (2003) Prognostic markers and criteria to initiate therapy in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s macroglobulinemia. Semin Oncol 30:116–120PubMedCrossRefGoogle Scholar
- 14.Chen CI, Kouroukis CT, White D, Voralia M, Stadtmauer E, Stewart AK et al (2007) Bortezomib is active in patients with untreated or relapsed Waldenstro¨ms macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:1570–1575PubMedCrossRefGoogle Scholar
- 18.Albanell J, Baselga J, Guix M et al (2003) Phase I study of bortezomib in combination with docetaxel in anthracycline-pretreated advanced breast cancer. Proc Am Soc Clin Oncol 22:16Google Scholar
- 39.Buske C, Hoster E, Dreyling M et al (2009) The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia 23:153–161PubMedCrossRefGoogle Scholar