Marqués Marta, Sorolla Maria Alba, Urdanibia Izaskun, Parisi Eva, Hidalgo Iván, Morales Serafín, Salud Antonieta, Sorolla Anabel
Research Group of Cancer Biomarkers, Lleida Institute for Biomedical Research Dr. Pifarré Foundation (IRBLleida), Av. Alcalde Rovira Roure, 80, 25198 Lleida, Spain.
Department of Medicine, University of Lleida, Av. Alcalde Rovira Roure, 80, 25198 Lleida, Spain.
Cancers (Basel). 2022 Feb 22;14(5):1101. doi: 10.3390/cancers14051101.
Breast cancer (BC) is the most diagnosed cancer worldwide and one of the main causes of cancer deaths. BC is a heterogeneous disease composed of different BC intrinsic subtypes such as triple-negative BC (TNBC), which is one of the most aggressive subtypes and which lacks a targeted therapy. Recent comprehensive analyses across cell types and cancer types have outlined a vast network of protein-protein associations between transcription factors (TFs). Not surprisingly, protein-protein networks central to oncogenesis and disease progression are highly altered during TNBC pathogenesis and are responsible for the activation of oncogenic programs, such as uncontrollable proliferation, epithelial-to-mesenchymal transition (EMT) and stemness. From the therapeutic viewpoint, inhibiting the interactions between TFs represents a very significant challenge, as the contact surfaces of TFs are relatively large and featureless. However, promising tools have emerged to offer a solution to the targeting problem. At the clinical level, some TF possess diagnostic and prognostic value in TNBC. In this review, we outline the recent advances in TFs relevant to TNBC growth and progression. Moreover, we highlight different targeting approaches to inhibit these TFs. Furthermore, the validity of such TFs as clinical biomarkers has been explored. Finally, we discuss how research is likely to evolve in the field.
乳腺癌（BC）是全球诊断率最高的癌症，也是癌症死亡的主要原因之一。BC是一种异质性疾病，由不同的BC内在亚型组成，如三阴性乳腺癌（TNBC），它是最具侵袭性的亚型之一，且缺乏靶向治疗。最近对不同细胞类型和癌症类型的综合分析勾勒出了转录因子（TFs）之间庞大的蛋白质-蛋白质相互作用网络。不出所料，在TNBC发病机制过程中，对肿瘤发生和疾病进展至关重要的蛋白质-蛋白质网络发生了高度改变，并导致致癌程序的激活，如无法控制的增殖、上皮-间质转化（EMT）和干性。从治疗角度来看，抑制TFs之间的相互作用是一项极具挑战性的任务，因为TFs的接触面相对较大且无特征。然而，已经出现了一些有前景的工具来解决靶向问题。在临床层面，一些TFs在TNBC中具有诊断和预后价值。在本综述中，我们概述了与TNBC生长和进展相关的TFs的最新进展。此外，我们强调了抑制这些TFs的不同靶向方法。此外，还探讨了此类TFs作为临床生物标志物的有效性。最后，我们讨论了该领域研究可能的发展方向。
