Combination of Alisertib and TAK-228 in Triple-Negative Breast Cancer
By: Andrew Goldstein
Posted: Friday, November 17, 2017
The combination of alisertib and TAK-228 yielded greater antiproliferative and proapoptotic activity in triple-negative breast cancer cells than either treatment individually, according to preclinical study data (Abstract B175) presented at the 2017 American Association for Cancer Research–National Cancer Institute–European Organisation for Research and Treatment of Cancer (AACR-NCI-EORTC) International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia by Jennifer R. Diamond, MD, of the University of Colorado Anschutz Medical Campus, Aurora.
Alisertib inhibits Aurora kinase A, which often is overexpressed in a wide variety of cancers, including breast and colon cancers. TAK-228 (formerly known as MLN0128) is a dual inhibitor of TORC1/2; TORC1 and TORC2 are upregulated in some tumors and appear to play a key role in the PI3K/Akt/mTOR signaling pathway, which is often dysregulated in human cancers.
Dr. Diamond and colleagues reported that the investigational combination resulted in greater inhibition of tumor cell growth in vivo than either single agent alone and simultaneous apoptosis. A phase I dose-escalation trial of this combination treatment is being conducted in patients with advanced solid tumors and metastatic triple-negative breast cancer (ClinicalTrials.gov identifier NCT02719691).