Epithelial-Mesenchymal Transition (EMT) as a Therapeutic Target

Abstract

Metastasis is the spread of cancer cells from the primary tumour to distant sites and organs throughout the body. It is the primary cause of cancer morbidity and mortality, and is estimated to account for 90% of cancer-related deaths. During the initial steps of the metastatic cascade, epithelial cancer cells undergo an epithelial-mesenchymal transition (EMT), and as a result become migratory and invasive mesenchymal-like cells while acquiring cancer stem cell properties and therapy resistance. As EMT is involved in such a broad range of processes associated with malignant transformation, it has become an increasingly interesting target for the development of novel therapeutic strategies. Anti-EMT therapeutic strategies could potentially not only prevent the invasion and dissemination of cancer cells, and as such prevent the formation of metastatic lesions, but also attenuate cancer stemness and increase the effectiveness of more classical chemotherapeutics. In this review, we give an overview about the pros and cons of therapies targeting EMT and discuss some already existing candidate drug targets and high-throughput screening tools to identify novel anti-EMT compounds.

Dynamic EMT: a multi‐tool for tumor progression

“…Several molecules to target EMT have been or are currently in clinical trials whereas others are already in use. These include blocking of upstream pathways which promote tumorigenesis also beyond EMT by ligand-neutralizing antibodies, decoy receptors or inhibitors to block TGFb, NF-jB, EGFR, c-MET, WNT and Notch signaling (comprehensively reviewed in (Redfern et al, 2018;Dudas et al, 2020;Jonckheere et al, 2021). Due to difficulties in targeting transcription factors, i.e., EMT-TFs, directly, another promising approach is to apply modified synthetic miRNAs that interfere with EMT-TFs on a posttranscriptional level.…”

“…Several molecules to target EMT have been or are currently in clinical trials whereas others are already in use. These include blocking of upstream pathways which promote tumorigenesis also beyond EMT by ligand‐neutralizing antibodies, decoy receptors or inhibitors to block TGFβ, NF‐κB, EGFR, c‐MET, WNT and Notch signaling (comprehensively reviewed in (Redfern et al , 2018 ; Dudas et al , 2020 ; Jonckheere et al , 2021 ).…”

Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

“…Epithelial-to-mesenchymal transition (EMT) is a process that occurs under normal physiologic conditions such as embryonic development and wound healing. During EMT, epithelial cells lose their polarity and acquire mesenchymal-like features along with the capacity to migrate and invade other tissues ( 108 ). An increasing number of studies have reported that the change in the oxygen level in cancer microenvironments and the HIF1α-induced hypoxia signal transduction pathway acted as a vital regulator of EMT, which played a key role in hypoxia-induced cancer invasion and metastasis ( 109 , 110 ).…”

Epithelial-to-Mesenchymal Transition in Fibrosis: Concepts and Targeting Strategies

“…This review aims to present the overview of recent concepts in EMT as well as novel insights as emerged from single cell transcriptomics, and to provide a summary of the strategies attempted to target EMT in the context of fibrotic diseases. So far, multiple approaches have been proposed to target EMT: from targeting the upstream inducing signaling pathways [which has been extensively reviewed in other recent reviews ( Di Gregorio et al, 2020 ; Jonckheere et al, 2021 )] to targeting EMT-transcription factors (TFs), promoting MET, and targeting EMT-induced vulnerabilities, the last being the strategy potentially leading to the most promising outcomes.…”