Bortezomib-induced pro-inflammatory macrophages limiting its anti-cancer efficacy

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 Multiple myeloma is a chronic progressive malignancy of plasma cells. Although treatment with the novel proteasome inhibitor, bortezomib, significantly improves patient survival, some patients fail to respond due to the development of de novo resistance. Uncovering tumor relapse mechanisms will lead to developing new and better cancer therapies.

In a study published in The Journal of Pathology, research team led by Professor Shaked from Technion-Israel Institute of Technology in Israel shows that tumor relapse occurs when the body, in effect, mobilizes itself in favor of the tumor, causing recurrence of the disease, increasing its aggressiveness and creating metastases or tumor spread. Even selective, highly focused treatments that harm cancer cells almost exclusively lead to a similar response.

In their study, plasma from bortezomib-treated mice significantly increases migration, viability and proliferation of Multiple myeloma cells in vitro, compared to plasma from vehicle treated mice. In vivo, bortezomib induces the mobilization of pro-angiogenic bone marrow cells. bortezomib promotes pro-inflammatory macrophages which account for MM cell aggressiveness, an effect which is partially mediated by interleukin-16. Accordingly, co-inoculation of multiple myeloma cells with pro-inflammatory macrophages from bortezomib-treated mice accelerates MM disease progression. The authors suggest that, in addition to the known effective anti-tumour activity of bortezomib, host-driven pro-tumorigenic effects generated in response to treatment can promote multiple myeloma aggressiveness, and thus may contribute to the overall limited efficacy. Future studies will focus on reducing the pro-tumorigenic host-mediated effects which contribute to tumour re-growth and metastasis, and improving anti-tumour efficacy 

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Bortezomib-induced pro-inflammatory macrophages as a potential factor limiting anti-tumour efficacy. Beyar-Katz O, Magidey K, Ben-Tsedek N, Alishekevitz D, Timaner M, Miller V, Lindzen M, Yarden Y, Avivi I, Shaked Y. J Pathol. 2016;239(3):262-73. 


  Go To Journal of Pathology