New Approaches in Modulating Transcription Factors for Cancer Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 2473

Special Issue Editor

Department of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH 03824, USA
Interests: breast and ovarian cancer; drug discovery; transcription factors; metastasis; chemoresistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aberrant expression or activation of transcription factors occurs in most cancers. Transcription factors are often the convergence point from many upstream signals that may be mutated or overexpressed in cancer, leading to inappropriate expression or constitutive activation. These transcription factors often promote the pathogenic features of cancer, and most cancers become addicted to the constitutive activity of the transcription factor. However, most transcription factors are often difficult to target, since many of them lack a ligand binding or active site. In this Special Issue, we will focus on new treatment modalities that target transcription factors in cancer. These strategies may include new small molecule inhibitors, CRISPR-based strategies, degrader technology, peptide mimetics, or others. 

Dr. Sarah Walker
Guest Editor

Manuscript Submission Information

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Keywords

  • transcription factors
  • cancer
  • treatment
  • degraders
  • inhibitors

Published Papers (1 paper)

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Research

19 pages, 4679 KiB  
Article
Drug Inhibition of Redox Factor-1 Restores Hypoxia-Driven Changes in Tuberous Sclerosis Complex 2 Deficient Cells
by Jesse D. Champion, Kayleigh M. Dodd, Hilaire C. Lam, Mohammad A. M. Alzahrani, Sara Seifan, Ellie Rad, David Oliver Scourfield, Melissa L. Fishel, Brian L. Calver, Ann Ager, Elizabeth P. Henske, David Mark Davies, Mark R. Kelley and Andrew R. Tee
Cancers 2022, 14(24), 6195; https://doi.org/10.3390/cancers14246195 - 15 Dec 2022
Viewed by 2215
Abstract
Therapies with the mechanistic target of rapamycin complex 1 (mTORC1) inhibitors are not fully curative for tuberous sclerosis complex (TSC) patients. Here, we propose that some mTORC1-independent disease facets of TSC involve signaling through redox factor-1 (Ref-1). Ref-1 possesses a redox signaling activity [...] Read more.
Therapies with the mechanistic target of rapamycin complex 1 (mTORC1) inhibitors are not fully curative for tuberous sclerosis complex (TSC) patients. Here, we propose that some mTORC1-independent disease facets of TSC involve signaling through redox factor-1 (Ref-1). Ref-1 possesses a redox signaling activity that stimulates the transcriptional activity of STAT3, NF-kB, and HIF-1α, which are involved in inflammation, proliferation, angiogenesis, and hypoxia, respectively. Here, we demonstrate that redox signaling through Ref-1 contributes to metabolic transformation and tumor growth in TSC cell model systems. In TSC2-deficient cells, the clinically viable Ref-1 inhibitor APX3330 was effective at blocking the hyperactivity of STAT3, NF-kB, and HIF-1α. While Ref-1 inhibitors do not inhibit mTORC1, they potently block cell invasion and vasculature mimicry. Of interest, we show that cell invasion and vasculature mimicry linked to Ref-1 redox signaling are not blocked by mTORC1 inhibitors. Metabolic profiling revealed that Ref-1 inhibitors alter metabolites associated with the glutathione antioxidant pathway as well as metabolites that are heavily dysregulated in TSC2-deficient cells involved in redox homeostasis. Therefore, this work presents Ref-1 and associated redox-regulated transcription factors such as STAT3, NF-kB, and HIF-1α as potential therapeutic targets to treat TSC, where targeting these components would likely have additional benefits compared to using mTORC1 inhibitors alone. Full article
(This article belongs to the Special Issue New Approaches in Modulating Transcription Factors for Cancer Therapy)
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