Title:The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Volume: 17
Issue: 3
Author(s): Lei Zhang, Mengyang Wu, Ruicong Su, Di Zhang*Guilian Yang*
Affiliation:
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
- Jilin Provincial Engineering
Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, 130118, China
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
- Jilin Provincial Engineering
Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, 130118, China
Keywords:
Proteasome, proteasome inhibitors, bortezomib, solid tumor, cell cycle, apoptosis, metastasis, angiogenesis, combination chemotherapy.
Abstract:
Background: The ubiquitin-proteasome system (UPS) is critical in cellular protein
degradation and widely involved in the regulations of cancer hallmarks. Targeting the UPS pathway
has emerged as a promising novel treatment in hematological malignancies and solid tumors.
Objective: This review mainly focuses on the preclinical results of proteasome inhibitors in solid
tumors.
Methods: We analyzed the published articles associated with the anticancer results of proteasome
inhibitors alone or combination chemotherapy in solid tumors. Important data presented in abstract
form were also discussed in this review.
Results/Conclusion: Proteasome inhibitors, such as bortezomib and carfilzomib, are highly effective
in treating solid tumors. The anticancer efficacy is not limited to affect the proteasomal inhibition-
associated signaling pathways but also widely involves the signaling pathways related to cell
cycle, apoptosis, and epithelial-mesenchymal transition (EMT). In addition, proteasome inhibitors
overcome the conventional chemo-resistance of standard chemotherapeutics by inhibiting signaling
pathways, such as NF-κB or PI3K/Akt. Combination chemotherapy of proteasome inhibitors and
standard chemotherapeutics are widely investigated in multiple relapsed or chemo-resistant solid tumor
types, such as breast cancer and pancreatic cancer. The proteasome inhibitors re-sensitize the
standard chemotherapeutic regimens and induce synergistic anticancer effects. The development of
novel proteasome inhibitors and delivery systems also improves the proteasome inhibitors’ anticancer
efficacy in solid tumors. This review summarizes the current preclinical results of proteasome
inhibitors in solid tumors and reveals the potential anticancer mechanisms.
