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Cancer Chemother Pharmacol. 2018 Feb;81(2):227-243. doi: 10.1007/s00280-017-3489-0. Epub 2017 Nov 28.

Positioning of proteasome inhibitors in therapy of solid malignancies.

Author information

1
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
2
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands. j.cloos@vumc.nl.
3
Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands. j.cloos@vumc.nl.
4
Amsterdam Rheumatology and Immunology Center, Location VUmc, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

Targeting of the protein degradation pathway, in particular, the ubiquitin-proteasome system, has emerged as an attractive novel cancer chemotherapeutic modality. Although proteasome inhibitors have been most successfully applied in the treatment of hematological malignancies, they also received continuing interest for the treatment of solid tumors. In this review, we summarize the current positioning of proteasome inhibitors in the treatment of common solid malignancies (e.g., lung, colon, pancreas, breast, and head and neck cancer), addressing topics of their mechanism(s) of action, predictive factors and molecular mechanisms of resistance.

KEYWORDS:

Bortezomib; Carfilzomib; Drug resistance; Proteasome inhibitors; Solid tumors

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