Alisertib, TAK-228 Combo Shows Promise for Treating Triple-Negative Breast Cancer

Alisertib, TAK-228 Combo Shows Promise for Treating Triple-Negative Breast Cancer
New data presented at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting, in Philadelphia, demonstrated that using alisertib along with TAK-228, two of Takeda's investigational therapies, was more effective in patients with triple-negative breast cancer and solid tumors than either treatment individually. The data come from two different studies conducted at the University of Colorado Cancer Center. The first, "Rational combination of mTOR and Aurora kinase A inhibition in preclinical models of triple-negative breast cancer," was a laboratory study. It provided the basis for the second study, "A phase Ib study of the combination of MLN0128 (dual TORC1/2 inhibitor) and MLN8237 (Aurora A inhibitor, alisertib) in patients with advanced solid tumors," a Phase 1 dose-escalation trial in patients with advanced solid tumors. Prior studies have shown that a protein called Aurora A plays a role in the development of breast cancer. Thus, a treatment called alisertib, which inhibits this protein, was developed to fight the disease. In some cancers, alisertib has the ability to kill cells. But in the case of triple-negative breast cancer, it causes a sleep-like state called senescence. In senescence, cancer cells stop growing quickly but don’t die. While achieving senescence in tumor cells can be good, killing the cancer cells is better. In the first study, researchers have shown that when treated with alisertib, the triple-negative breast cancer cells increase a pathway called mTOR, which allows these cells to survive. "Unfortunately, even in this senescent state, triple-negative breast cancer cells can signal their neighbors to grow," Jennifer Diamond, MD, who presented both studies at the meeting, said in a press release. "The first study w
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