Inhibition of protein translational machinery in triple-negative breast cancer as a promising therapeutic strategy
Arpit Dheeraj, Fernando Jose Garcia-Marques, Dhanir Tailor, Abel Bermudez, Angel Resendez, Mallesh Pandrala, Benedikt W. Grau, Praveen Kumar, Carrsyn B. Haley, Alexander Honkala, Praveen Kumar Kujur, Stefanie S. Jeffrey, Sharon J. Pitteri, Sanjay V. Malhotra
Abstract
Y-box binding protein-1 (YB-1) is a proto-oncogenic protein associated with protein translation regulation. It plays a crucial role in the development and progression of triple-negative breast cancer (TNBC). In this study, we describe a promising approach to inhibit YB-1 using SU056, a small-molecule inhibitor. SU056 physically interacts with YB-1 and reduces its expression, which helps to restrain the progression of TNBC. Proteome profiling analysis indicates that the inhibition of YB-1 by SU056 can alter the proteins that regulate protein translation, an essential process for cancer cell growth. Preclinical studies on human cells, mice, and patient-derived xenograft tumor models show the effectiveness of SU056. Moreover, toxicological studies have shown that SU056 treatment and dosing are well tolerated without any adverse effects. Overall, our study provides a strong foundation for the further development of SU056 as a potential treatment option for patients with TNBC by targeting YB-1.