dc.contributor.author |
Giliberto, M
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dc.contributor.author |
Thimiri Govindaraj, Deepak B
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dc.contributor.author |
Cremaschi, A
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dc.contributor.author |
Skånland, SS
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dc.contributor.author |
Gade, A
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dc.contributor.author |
Tjønnfjord, GE
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dc.contributor.author |
Schjesvold, F
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dc.contributor.author |
Munthe, LA
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dc.contributor.author |
Taskén, K
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dc.date.accessioned |
2022-05-09T08:28:08Z |
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dc.date.available |
2022-05-09T08:28:08Z |
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dc.date.issued |
2022-03 |
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dc.identifier.citation |
Giliberto, M., Thimiri Govindaraj, D.B., Cremaschi, A., Skånland, S., Gade, A., Tjønnfjord, G., Schjesvold, F. & Munthe, L. et al. 2022. Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically. <i>Molecular Oncology, 16(6).</i> http://hdl.handle.net/10204/12407 |
en_ZA |
dc.identifier.issn |
1574-7891 |
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dc.identifier.issn |
1878-0261 |
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dc.identifier.uri |
doi: 10.1002/1878-0261.13191
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|
dc.identifier.uri |
http://hdl.handle.net/10204/12407
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|
dc.description.abstract |
The management of multiple myeloma (MM) is challenging: An assortment of available drug combinations adds complexity to treatment selection, and treatment resistance frequently develops. Given the heterogeneous nature of MM, personalized testing tools are required to identify drug sensitivities. To identify drug sensitivities in MM cells, we established a drug testing pipeline to examine ex vivo drug responses. MM cells from 44 patients were screened against 30 clinically relevant single agents and 44 double- and triple-drug combinations. We observed variability in responses across samples. The presence of gain(1q21) was associated with low sensitivity to venetoclax, and decreased ex vivo responses to dexamethasone reflected the drug resistance observed in patients. Less heterogeneity and higher efficacy was detected with many combinations compared to the corresponding single agents. We identified new synergistic effects of melflufen plus panobinostat using low concentrations (0.1-10 nm and 8 nm, respectively). In agreement with clinical studies, clinically approved combinations, such as triple combination of selinexor plus bortezomib plus dexamethasone, acted synergistically, and synergies required low drug concentrations (0.1 nm bortezomib, 10 nm selinexor and 4 nm dexamethasone). In summary, our drug screening provided results within a clinically actionable 5-day time frame and identified synergistic drug efficacies in patient-derived MM cells that may aid future therapy choices. |
en_US |
dc.format |
Fulltext |
en_US |
dc.language.iso |
en |
en_US |
dc.relation.uri |
https://pubmed.ncbi.nlm.nih.gov/35148457/ |
en_US |
dc.source |
Molecular Oncology, 16(6) |
en_US |
dc.subject |
Drug combinations |
en_US |
dc.subject |
Ex vivo drug sensitivit |
en_US |
dc.subject |
Gain(1q21) |
en_US |
dc.subject |
Patient-derived MM cells |
en_US |
dc.subject |
Precision medicine |
en_US |
dc.subject |
Synergy |
en_US |
dc.title |
Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically |
en_US |
dc.type |
Article |
en_US |
dc.description.pages |
1241-1258 |
en_US |
dc.description.note |
Copyright: 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
en_US |
dc.description.cluster |
Next Generation Health |
en_US |
dc.description.impactarea |
Synthetic Nanobiotech Biomachs |
en_US |
dc.identifier.apacitation |
Giliberto, M., Thimiri Govindaraj, D. B., Cremaschi, A., Skånland, S., Gade, A., Tjønnfjord, G., ... Taskén, K. (2022). Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically. <i>Molecular Oncology, 16(6)</i>, http://hdl.handle.net/10204/12407 |
en_ZA |
dc.identifier.chicagocitation |
Giliberto, M, Deepak B Thimiri Govindaraj, A Cremaschi, SS Skånland, A Gade, GE Tjønnfjord, F Schjesvold, LA Munthe, and K Taskén "Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically." <i>Molecular Oncology, 16(6)</i> (2022) http://hdl.handle.net/10204/12407 |
en_ZA |
dc.identifier.vancouvercitation |
Giliberto M, Thimiri Govindaraj DB, Cremaschi A, Skånland S, Gade A, Tjønnfjord G, et al. Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically. Molecular Oncology, 16(6). 2022; http://hdl.handle.net/10204/12407. |
en_ZA |
dc.identifier.ris |
TY - Article
AU - Giliberto, M
AU - Thimiri Govindaraj, Deepak B
AU - Cremaschi, A
AU - Skånland, SS
AU - Gade, A
AU - Tjønnfjord, GE
AU - Schjesvold, F
AU - Munthe, LA
AU - Taskén, K
AB - The management of multiple myeloma (MM) is challenging: An assortment of available drug combinations adds complexity to treatment selection, and treatment resistance frequently develops. Given the heterogeneous nature of MM, personalized testing tools are required to identify drug sensitivities. To identify drug sensitivities in MM cells, we established a drug testing pipeline to examine ex vivo drug responses. MM cells from 44 patients were screened against 30 clinically relevant single agents and 44 double- and triple-drug combinations. We observed variability in responses across samples. The presence of gain(1q21) was associated with low sensitivity to venetoclax, and decreased ex vivo responses to dexamethasone reflected the drug resistance observed in patients. Less heterogeneity and higher efficacy was detected with many combinations compared to the corresponding single agents. We identified new synergistic effects of melflufen plus panobinostat using low concentrations (0.1-10 nm and 8 nm, respectively). In agreement with clinical studies, clinically approved combinations, such as triple combination of selinexor plus bortezomib plus dexamethasone, acted synergistically, and synergies required low drug concentrations (0.1 nm bortezomib, 10 nm selinexor and 4 nm dexamethasone). In summary, our drug screening provided results within a clinically actionable 5-day time frame and identified synergistic drug efficacies in patient-derived MM cells that may aid future therapy choices.
DA - 2022-03
DB - ResearchSpace
DP - CSIR
J1 - Molecular Oncology, 16(6)
KW - Drug combinations
KW - Ex vivo drug sensitivit
KW - Gain(1q21)
KW - Patient-derived MM cells
KW - Precision medicine
KW - Synergy
LK - https://researchspace.csir.co.za
PY - 2022
SM - 1574-7891
SM - 1878-0261
T1 - Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically
TI - Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically
UR - http://hdl.handle.net/10204/12407
ER -
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en_ZA |
dc.identifier.worklist |
25638 |
en_US |