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2015 ; 5
(ä): 189
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gab.com Text
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English Wikipedia
Scientific Rationale Supporting the Clinical Development Strategy for the
Investigational Aurora A Kinase Inhibitor Alisertib in Cancer
#MMPMID26380220
Niu H
; Manfredi M
; Ecsedy JA
Front Oncol
2015[]; 5
(ä): 189
PMID26380220
show ga
Alisertib (MLN8237) is a selective small molecule inhibitor of Aurora A kinase
that is being developed in multiple cancer indications as a single agent and in
combination with other therapies. A significant amount of research has elucidated
a role for Aurora A in orchestrating numerous activities of cells transiting
through mitosis and has begun to shed light on potential non-mitotic roles for
Aurora A as well. These biological insights laid the foundation for multiple
clinical trials evaluating the antitumor activity of alisertib in both solid
cancers and heme-lymphatic malignancies. Several key facets of Aurora A biology
as well as empirical data collected in experimental systems and early clinical
trials have directed the development of alisertib toward certain cancer types,
including neuroblastoma, small cell lung cancer, neuroendocrine prostate cancer,
atypical teratoid/rhabdoid tumors, and breast cancer among others. In addition,
these scientific insights provided the rationale for combining alisertib with
other therapies, including microtubule perturbing agents, such as taxanes, EGFR
inhibitors, hormonal therapies, platinums, and HDAC inhibitors among others.
Here, we link the key aspects of the current clinical development of alisertib to
the originating scientific rationale and provide an overview of the alisertib
clinical experience to date.