Everolimus Shows Synergistic Antimyeloma Effects with Bortezomib via the AKT/mTOR Pathway
Abstract
Multiple myeloma (MM) is characterized by the proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraproteins (M proteins). Everolimus works similarly to sirolimus as a mammalian target of rapamycin (mTOR) inhibitor. Bortezomib was the first therapeutic proteasome inhibitor to be tested in humans with MM. However, the combination of these two drugs for the treatment of MM has been rarely reported. In this study, we compared the therapeutic effects of everolimus and bortezomib, as well as those of a combination of everolimus and bortezomib, using an in vitro MM cell line model and in vivo xenograft mouse model. Our results showed that the synergistic antitumor effects of everolimus and bortezomib have significant inhibitory effect through inhibition of the AKT/mTOR pathway in both the MM cell lines and MM-bearing mice model. Our results provided evidence that the mTOR inhibitor, everolimus, will be a potential drug in MM therapy.
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Everolimus combined with bortezomib has a significant inhibitory effect on MM cells.
“Everolimus, another mTOR inhibitor similar to temsirolimus, has been evaluated in combination with bortezomib for its inhibitory effects on MM tumor cells. Studies have shown that this combination therapy has a significant inhibitory effect on MM cells, indicating the potential of everolimus as a treatment option for MM patients [69].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [69]
Cites
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Multiple myeloma: signaling pathways and targeted therapy
Lu, Q., Yang, D., Li, H., Niu, T., & Tong, A. (2024) · Molecular biomedicine · doi:10.1186/s43556-024-00188-w · Cited by 90 · see citing works
The Rationale for the Dual-Targeting Therapy for RSK2 and AKT in Multiple Myeloma
Isa, R., Horinaka, M., Tsukamoto, T., Mizuhara, K., Fujibayashi, Y., Taminishi-Katsuragawa, Y., Okamoto, H., Yasuda, S., Kawaji-Kanayama, Y., Matsumura-Kimoto, Y., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23062919 · Cited by 11 · see citing works
- Authors
- Li, J., Liu, Z., Li, Y., Jing, Q., Wang, H., Liu, H., Chen, J., Feng, J., Shao, Q., & Fu, R.
- Affiliations
- Tianjin Medical University General Hospital (CN)
- Corresponding author
- Fu, Rong
- Venue
- Journal of Investigative Medicine
- Publisher
- SAGE Publications
- Published
- 2019-01
- Volume
- 67
- Issue
- 1
- Pages
- 39-47
- ISSN
- 1081-5589 (ISSN-L)
- 1708-8267
- OpenAlex
- W2862261274
- Cited by
- 15
- References
- 2
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 3
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Investigative Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- multiple myeloma, everolimus, bortezomib, combination therapy, Akt/mTOR signaling, mTOR inhibition, proteasome inhibitors, synergistic antitumor effect, plasma cell proliferation, xenograft mouse model
- MeSH terms
- Everolimus, Bortezomib, Animals, Antineoplastic Combined Chemotherapy Protocols, Cell Survival, Drug Synergism, Mice, Nude, Multiple Myeloma, Signal Transduction, Apoptosis, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases
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