Putting the BRK on breast cancer: From molecular target to therapeutics

Abstract

BR east tumor K inase (BRK, also known as PTK6) is a non-receptor tyrosine kinase that is highly expressed in breast carcinomas while having low expression in the normal mammary gland, which hints at the oncogenic nature of this kinase in breast cancer. In the past twenty-six years since the discovery of BRK, an increasing number of studies have strived to understand the cellular roles of BRK in breast cancer. Since then, BRK has been found both in vitro and in vivo to activate a multitude of oncoproteins to promote cell proliferation, metastasis, and cancer development. The compelling evidence concerning the oncogenic roles of BRK has also led, since then, to the rapid and exponential development of inhibitors against BRK. This review highlights recent advances in BRK biology in contributing to the “hallmarks of cancer”, as well as BRK's therapeutic significance. Importantly, this review consolidates all known inhibitors of BRK activity and highlights the connection between drug action and BRK-mediated effects. Despite the volume of inhibitors designed against BRK, none have progressed into clinical phase. Understanding the successes and challenges of these inhibitor developments are crucial for the future improvements of new inhibitors that can be clinically relevant.

PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation

“…PTK6 is a tyrosine kinase, which consists of three protein domains (a classic src homology 3 (SH3) domains, a src homology 2 (SH2) domain, and a tyrosine kinase (SH1) domain). The protein domains of PTK6 are usually involved in protein-protein interactions [ 21 ]. Firstly, we obtained 55 proteins that might bind to PTK6 by the BioGRID database (Fig.…”

“…To analyze the mechanism of autophagy in UM, protein tyrosine kinase 6 (PTK6) was screened from the Cancer Genome Atlas (TCGA) database through the prognosis of melanoma patients and the difference of protein expression in UM. PTK6, also known as breast tumor kinase (BRK), is a nonreceptor intracellular tyrosine kinase cloned from metastatic breast cancers that can promote the differentiation of normal epithelial cells [20,21]. PTK6 can promote tumorigenesis of breast cancer, lung cancer, colorectal cancer, and other tumors [22][23][24].…”

FSCN1 Promotes Esophageal Carcinoma Progression Through Downregulating PTK6 via its RNA-Binding Protein Effect

“…PTK6, also known as breast tumor kinase, was originally identified in human breast tumors ( Mitchell et al, 1994 ). PTK6 is low to undetectable in normal tissues and is highly expressed in numerous tumors, such as breast, cervix, and ovary ( Schmandt et al, 2006 ; Ito et al, 2016 ; Wang et al, 2016 ; Ang et al, 2021 ). In ESCC, PTK6 expression was found to be lower in tumors than in peritumoral esophageal tissues ( Chen et al, 2014 ).…”

Epidemiología Y Nuevas Dianas Moleculares en Cáncer De Mama

“…Los anticuerpos biespecificos se adhieren al receptor diana de interés e inducen la activación de las células T, la localización en el tumor y la proliferación policlonal a través de la interacción instantánea con el dominio CD3 de las células T (38). Otra diana terapéutica que hoy en día se está estudiando es el papel oncogénico de BRK en las características del cáncer, por ende, es de gran aporte que se encuentre el potencial de BRK para la creación y desarrollo de nuevos tratamientos para combatir el cáncer de mama (24). Por otro lado, una terapia sistémica adyuvante que consiste en ensayos genómicos, está favoreciendo al oncólogo clínico en la toma de decisiones; esta abarca dos ensayos reconocidos, las cuales son el Oncotype DX y el Microarray en curso en la patología con ganglios negativos (53).…”