scholarly journals Therapeutic targeting of oncogenic transcription factors by natural products in eye cancer

2018 ◽  
Vol 129 ◽  
pp. 365-374 ◽  
Author(s):  
Michelle G. Zhang ◽  
John Y. Lee ◽  
Ryan A. Gallo ◽  
Wensi Tao ◽  
David Tse ◽  
...  
Keyword(s):  
Natural Products ◽  
Transcription Factors ◽  
Therapeutic Targeting

scholarly journals EMT-Inducing Transcription Factors, Drivers of Melanoma Phenotype Switching, and Resistance to Treatment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2154 ◽  
Author(s):  
Yaqi Tang ◽  
Simon Durand ◽  
Stéphane Dalle ◽  
Julie Caramel
Keyword(s):  
Transcription Factors ◽  
Neural Crest ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Specific Expression ◽  
Therapeutic Targeting ◽  
Mesenchymal Transition ◽  
Neural Crest Stem Cell ◽  
Resistance To Treatment ◽  
Phenotype Switching

Transcription factors, extensively described for their role in epithelial–mesenchymal transition (EMT-TFs) in epithelial cells, also display essential functions in the melanocyte lineage. Recent evidence has shown specific expression patterns and functions of these EMT-TFs in neural crest-derived melanoma compared to carcinoma. Herein, we present an update of the specific roles of EMT-TFs in melanocyte differentiation and melanoma progression. As major regulators of phenotype switching between differentiated/proliferative and neural crest stem cell-like/invasive states, these factors appear as major drivers of intra-tumor heterogeneity and resistance to treatment in melanoma, which opens new avenues in terms of therapeutic targeting.

scholarly journals Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Clarissa S. Santoso ◽  
Zhaorong Li ◽  
Jaice T. Rottenberg ◽  
Xing Liu ◽  
Vivian X. Shen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cytokine Production ◽  
Lavage Fluid ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Rna Seq ◽  
Therapeutic Targeting ◽  
Inflammatory Cytokine Production ◽  
Approved Drugs ◽  
Fda Approved Drugs

Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drugs combinations on inflammatory cytokine production, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.

scholarly journals A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia

2021 ◽  
Author(s):  
Taku Harada ◽  
Yaser Heshmati ◽  
Jeremie Kalfon ◽  
Juliana Xavier Ferrucio ◽  
Monika Perez ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Transcription Factors ◽  
Myeloid Leukemia ◽  
Control Cell ◽  
Therapeutic Targeting ◽  
Genome Wide ◽  
Regulatory Module ◽  
Small Set ◽  
Evolving Model ◽  
Acute Myeloid

A small set of lineage-restricted transcription factors (TFs), termed core regulatory circuitry (CRC), control cell identity and malignant transformation. Here, we integrated gene dependency, chromatin architecture and TF perturbation datasets to characterize 31 core TFs in acute myeloid leukemia (AML). Contrary to a widely accepted model, we detected a modular CRC structure with hierarchically organized, partially redundant and only sparsely interconnected modules of core TFs controlling distinct genetic programs. Rapid TF degradation followed by measurement of genome-wide transcription rates revealed that core TFs directly regulate dramatically fewer genes than previously assumed. Leukemias carrying KMT2A (MLL) rearrangements depend on the IRF8/MEF2 axis to directly enforce expression of the key oncogenes MYC, HOXA9 and BCL2. Our datasets provide an evolving model of CRC organization in human cells, and a resource for further inquiries into and therapeutic targeting of aberrant transcriptional circuits in cancer.

Modulation of oncogenic transcription factors by bioactive natural products in breast cancer

2018 ◽  
Vol 128 ◽  
pp. 376-388 ◽  
Author(s):  
Mohadeseh Hasanpourghadi ◽  
Ashok Kumar Pandurangan ◽  
Mohd Rais Mustafa
Keyword(s):  
Breast Cancer ◽  
Natural Products ◽  
Transcription Factors ◽  
Bioactive Natural Products

scholarly journals Notch Inhibition in Cancer: Challenges and Opportunities

2020 ◽  
Vol 74 (10) ◽  
pp. 779-783 ◽  
Author(s):  
Doriano Fabbro ◽  
Michael Bauer ◽  
Maximilien Murone ◽  
Rajwinder Lehal
Keyword(s):  
Transcription Factors ◽  
Phase 1 ◽  
Target Dose ◽  
Therapeutic Targeting ◽  
Receptor Ligand ◽  
Oncogenic Pathway ◽  
Medical Need ◽  
Challenges And Opportunities ◽  
Notch Inhibition ◽  
First And Second Generation

Notch is a key oncogenic pathway in several human cancers and to date, no targeted treatment of Notch activated cancers is available to patients. Therapeutic targeting of Notch has been an unresolved challenge due to severe on-target dose limiting toxicities associated with pan-Notch inhibition by either γ-secretase inhibitors or receptor/ligand targeting MAbs. At Cellestia Biotech, we have identified novel series of small molecule inhibitors of the Notch transcription complex. These molecules act as pan-Notch inhibitors and do not cause toxicities commonly associated with first- and second-generation Notch inhibitors currently tested in the clinic, thus providing a novel and unique opportunity to address a high unmet medical need. Our lead molecule, CB-103 is currently being investigated in Phase-1 dose escalation in cancer patients. Cellestia Biothech is further expanding its medicinal chemistry activities advancing the development of novel molecules for targeting transcription factors in cancer as well as non-cancer indications.

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