In vitro anti-myeloma activity of the Aurora kinase inhibitor VE-465.
This study characterized the preclinical anti-myeloma activity of VE465, a low molecular weight pan-Aurora kinase inhibitor. After 96-h drug exposure, several multiple myeloma (MM) cell lines were more sensitive to VE465 compared to non-malignant cells. The anti-MM activity of VE465 was maintained in the presence of interleukin-6 and, interestingly, enhanced by co-culture with stromal cells. However, primary MM cells were less responsive than cell lines. Combinations with dexamethasone (Dex), doxorubicin (Doxo) and bortezomib showed no antagonism. Our study highlights the potential role of the tumour microenvironment in modulating the activity of this drug class.
Negri
Joseph M
JM
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
McMillin
Douglas W
DW
Delmore
Jake
J
Mitsiades
Nicholas
N
Hayden
Patrick
P
Klippel
Steffen
S
Hideshima
Teru
T
Chauhan
Dharminder
D
Munshi
Nikhil C
NC
Buser
Carolyn A
CA
Pollard
John
J
Richardson
Paul G
PG
Anderson
Kenneth C
KC
Mitsiades
Constantine S
CS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D064127:Aurora Kinases; D002450:Cell Communication / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
D000970:Antineoplastic Agents; D064127:Aurora Kinases; D010879:Piperazines; D017346:Protein Serine-Threonine Kinases; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines