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

Autor:	Dheeraj A; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, USA., Garcia Marques FJ; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA., Tailor D; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, USA., Bermudez A; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA., Resendez A; Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, USA., Pandrala M; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Grau B; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Kumar P; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Haley CB; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Honkala A; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Kujur P; Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA., Jeffrey SS; Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA., Pitteri S; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA., Malhotra SV; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: malhotsa@ohsu.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 May 21; Vol. 5 (5), pp. 101552. Date of Electronic Publication: 2024 May 09.
DOI:	10.1016/j.xcrm.2024.101552
Abstrakt:	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. Competing Interests: Declaration of interests S.V.M. is on the scientific advisory board of Cadila Pharmaceuticals Pvt., Ltd., and is a cofounder of Arxeon, Inc. A.D., D.T., and S.V.M are contributors to a US patent with application number 18/255,827,2024. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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