Are Transcription Factors Plausible Oncotargets for Triple Negative Breast Cancers?

Abstract

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.

Identification of Cholangiocarcinoma (CCA) Subtype-Specific Biomarkers

“…It is made colored). This discovery is consistent with the transcription profiling data reported in various cancer types [30][31][32][33][34], including HCC [31,35]. Recognizing the significant role of TFs in the progression of liver cancers [38][39][40][41][42], we conducted enrichment analyses to unveil the signaling pathways in which the identified TFs are implicated in the context of CCA.…”

“…Hence, mutated or improperly regulated TFs in different cancers serve as clear targets for therapeutic drugs as well as diagnostic and prognostic biomarkers [28,29]. Numerous new prognostic biomarkers or biomarker combinations derived from TFs have been identified through comprehensive omics analyses of transcription profiles across different cancer types [30][31][32][33][34], including HCC [31,35]. As numerous cases of liver cancer arise from chronic health conditions like cirrhosis triggered by hepatitis B or hepatitis C infections [18][19][20]22,23,[36][37][38], alterations in gene expression induced by viruses have been documented at both the DNA and RNA levels [38][39][40][41][42].…”

Applications of CRISPR Technology to Breast Cancer and Triple Negative Breast Cancer Research

“…Another relevant gene is BRCA1/2, which plays an important role in DNA double-strand break repair and DNA stability. It has been observed that the BRCA1 gene can be inactivated epigenetically in TNBC by promoter methylation, conferring poor prognosis [14,15]. Regarding the Phosphoinositide-3-kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) pathway, TNBC commonly presents PTEN mutations, whereas mutations in PI3KCA are less frequent.…”

“…Moreover, it has been described that 45% of the BRCA1-mutated TNBCs also harbour MYC amplification. Finally, the transcription factor FOXC1 is highly overexpressed in TNBC, where it has been reported to induce survival, proliferation, epithelial-to-mesenchymal transition (EMT), metastasis, invasiveness, and chemoresistance [14,17,18].…”

Designing a novel SOX9 based multi-epitope vaccine to combat metastatic triple-negative breast cancer using immunoinformatics approach

“…In particular, the SOX proteins SOX 9, SOX 10, SOX 2, SOX 4, SOX 8 and SOX 11 are reported to be overexpressed in TNBC. However, effective inhibition of these TFs remains elusive because of the absence of binding pockets and intracellular localization [ 12 , 13 ]. Meanwhile, scientific advancement has drawn attention to the development of vaccination strategy using these transcription factors.…”