Anti-tumor Efficacy and Safety of the BAG3/HSP70 Inhibitor YM-1 ina Triple Negative Breast Cancer Model

Abstract

Patients who treat with TNBC are usually with intense chemotherapy. Recently, BAG3 has been suggested as apotential therapeutic target for cancer. However, inhibiting BAG3 for therapy may result in unintended damage tocardiomyocytes. Thus, this research proposal will test whether or not the inhibition of BAG3 will significantly affectthe heart while still having potent anti-tumor efficacy. Human TNBC cell line BT-549 cells will be inoculated into CB17/SCID mice. When the tumor grows to 100 mm3, mice will be intraperitoneally injected with different doses of YM1, an inhibitor of BAG3/HSP70. The clinically used TNBC chemotherapy drug doxorubicin will be used as the positivecontrol. The tumor growth, expressed as the change in tumor volume and tumor growth inhibition percentage (TGI),will be measured. Troponin I level in the serum, ECG measurement, and Hematoxylin and Eosin staining will be used toassess heart damage. The results of our study will indicate whether the animals will tolerate the BAG3 inhibitor, YM-1,at its effective doses and whether inhibition of BAG3 may be a better option, particularly regarding unwanted effects oncardiomyopathy, compared to standard of care in TNBC. Future investigations are warranted.