Study could combat aggressive chemotherapy resistant TNBC

A Mount Sinai study titled Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease describes how a novel therapeutic (108600) combats aggressive chemotherapy-resistant triple-negative breast cancer (TBNC).

108600 targets and inhibits breast cancer stem cells, a subpopulation of cells found within patient triple negative breast cancers that can promote resistance to chemotherapy, making it less effective. 108600 overcomes chemotherapy resistance of patient triple negative breast cancer. In mouse models generated from patient cancers, 108600 in combination with chemotherapy eliminates aggressive triple negative breast cancer, even those that have already metastasised. Once translated to an early phase clinical trial, 108600 has the potential to improve survival and quality of life for patients diagnosed with triple negative breast cancer.

Chemotherapy resistant triple negative breast cancer is associated with early recurrence and progression to metastatic stage four disease. Breast cancer stem cells contribute to chemotherapy resistance and therapies that eliminate these stem cells would improve outcomes for high-risk patients.

Though TNBC makes up about 15-20% of newly diagnosed breast cancers in the US, there are still few FDA-approved targeted approaches for patients with this aggressive form of the disease. This is particularly concerning since TNBC disproportionately impacts younger women (those who are premenopausal), those with inherited mutations in the BRCA1 gene, and Black women—a group that has an alarming 40% higher rate of breast cancer mortality in the U.S.

Published in Nature Communications, the study is written by senior authors Hanna Irie (Associate Professor of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai) and  E. Premkumar Reddy (Professor of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai).

Co-author Dr Irie said: “Triple negative breast cancer is particularly challenging to treat because of the limited options beyond chemotherapy. There are fewer targeted therapies compared to other types of breast cancer. Many triple negative breast cancers also do not respond completely to our best chemotherapies for reasons that we are still trying to understand fully but cancer stem cells play an important role in this resistance.

“This study shows an exciting new therapeutic compound (108600) that can overcome chemotherapy resistance of triple negative breast cancer by targeting cancer stem cells that can drive this resistance. The study also shows how this drug can block and kill triple negative breast cancer that has already spread to other parts of the body, giving hope that this could be effective treatment for patients living with stage four triple negative breast cancer.”

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