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Therapeutic YY1 Inhibitors in Cancer: ALL in ONE
1Department of Microbiology, Immunology, & Molecular Genetics, David Geffen School of Medicine, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA.
Abstract:
Various targeted therapies for cancer have resulted in a significant prolongation of survival and a better quality of life. However, unfortunately, a small subset of cancer patients responds to such therapies initially and then develops resistance after the initial therapies. Based on resistant mechanisms, it should be possible to develop new and specific targeted therapies effective against unresponsive patients. Our investigations and those of others have identified a gene product, Yin Yang 1 (YY1), a transcription factor that is overexpressed in many cancers and that was shown to be involved in the regulation of cell survival, cell proliferation, cell invasion, metastasis, and resistance. Several studies showed that the inhibition of YY1 resulted in significant inhibition of the tumor phenotype and reversal of resistance. Examples of such YY1 inhibitors include siRNA YY1, nitric oxide donors, proteasome inhibitors, and inhibitors of activated survival pathways such as inhibitors of nuclear factor-kappa beta. However, there is still a need to develop specific and targeted inhibitors of YY1. In this review, a general discussion is provided on the role of YY1 overexpression in cancer and the application of various inhibitors of YY1 activities and their potential as therapeutics.
Insights
Yin Yang 1 (YY1) is overexpressed in many cancers and drives tumor growth and resistance. Inhibiting YY1 shows promise for overcoming cancer therapy resistance and developing new targeted treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Targeted cancer therapies improve survival but resistance develops in some patients.
- Understanding resistance mechanisms is crucial for developing effective treatments.
- Yin Yang 1 (YY1) is a transcription factor implicated in cancer progression and therapy resistance.
Purpose of the Study:
- To review the role of YY1 overexpression in various cancers.
- To discuss current and potential YY1 inhibitors as targeted cancer therapeutics.
- To highlight the need for specific YY1 inhibitors to overcome treatment resistance.
Main Methods:
- Literature review of studies on YY1 in cancer.
- Analysis of YY1's role in cell survival, proliferation, invasion, metastasis, and resistance.
- Examination of various YY1 inhibition strategies and their therapeutic potential.
Main Results:
- YY1 overexpression is linked to tumor progression and resistance across multiple cancer types.
- Inhibition of YY1 has demonstrated significant anti-tumor effects and reversal of resistance.
- Existing YY1 inhibitors include siRNA, nitric oxide donors, proteasome inhibitors, and pathway inhibitors.
Conclusions:
- YY1 is a critical target for overcoming cancer therapy resistance.
- Developing specific YY1 inhibitors is essential for effective cancer treatment.
- Targeting YY1 offers a promising therapeutic strategy for resistant cancers.
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