Aurora A Functional Single Nucleotide Polymorphism (SNP) Correlates With Clinical Outcome in Patients With Advanced Solid Tumors Treated With Alisertib, an Investigational Aurora A Kinase Inhibitor

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Niu, Huifeng | Shin, Hyunjin | Gao, Feng | Zhang, Jacob | Bahamon, Brittany | Danaee, Hadi | Melichar, Bohuslav | Schilder, Russell | Coleman, Robert | Falchook, Gerald | Adenis, Antoine | Behbakht, Kian | Demichele, Angela | Dees, Elizabeth Claire | Perez, Kimberly | Matulonis, Ursula | Sawrycki, Piotr | Huebner, Dirk | Ecsedy, Jeffrey

Edité par CCSD ; Elsevier -

International audience. BACKGROUND:Alisertib (MLN8237) is an investigational, oral, selective Aurora A kinase inhibitor. Aurora A contains two functional single nucleotide polymorphisms (SNPs; codon 31 [F/I] and codon 57 [V/I]) that lead to functional changes. This study investigated the prognostic and predictive significance of these SNPs.METHODS:This study evaluated associations between Aurora A SNPs and overall survival (OS) in The Cancer Genome Atlas (TCGA) database. The Aurora A SNPs were also evaluated as predictive biomarkers for clinical outcomes to alisertib in two phase 2 studies (NCT01045421 and NCT01091428). Aurora A SNP genotyping was obtained from 85 patients with advanced solid tumors receiving single-agent alisertib and 122 patients with advanced recurrent ovarian cancer treated with alisertib plus weekly paclitaxel (n=62) or paclitaxel alone (n=60). Whole blood was collected prior to treatment and genotypes were analyzed by PCR.

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