Inhibition of protein translational machinery in triple-negative breast cancer as a promising therapeutic strategy

抑制三阴性乳腺癌中的蛋白质翻译机制是一种有前途的治疗策略

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作者:Arpit Dheeraj, Fernando Jose Garcia Marques, Dhanir Tailor, Abel Bermudez, Angel Resendez, Mallesh Pandrala, Benedikt Grau, Praveen Kumar, Carrsyn B Haley, Alexander Honkala, Praveen Kujur, Stefanie S Jeffrey, Sharon 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.

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