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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Targeting transcription factors for cancer therapy
1Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medical Oncology, Mayer 522B, 44 Binney Street, Boston, MA 02115, USA. david_frank@dfci.harvard.edu
Abstract:
Despite all of the advances in understanding the operations of cancer cells, cancer is on track to pass heart disease as the leading cause of death in the developed world. The primary treatment approach for advanced cancer remains chemotherapeutic drugs that kill cells, both normal and malignant, in a relatively indiscriminate manner. One recent advance in treatment has been the introduction of drugs that target kinases, which can undergo mutations and become activated inappropriately in cancer cells. However, the maximal benefit that can derive from this approach may soon be reached, and a clear need exists for identifying other therapeutic targets that will have broader applicability. Transcription factors, proteins that regulate the expression of genes within a cell and ultimately control cell behavior, are frequently locked in an 'on' position in cancer cells; when the transcription factors are shut off, a cancer cell will generally stop growing or begin to die. In contrast, normal cells tolerate a loss of transcription factor function with little consequence, as a result of redundancies that are present under normal conditions. Despite challenges involved in developing drugs to target transcription factors, increasing evidence indicates that this approach may be a highly promising strategy in the development of cancer treatments that are more effective and less toxic than existing options.
Insights
Targeting transcription factors offers a promising new strategy for cancer treatment. These proteins control cell behavior, and inhibiting them can stop cancer growth with potentially fewer side effects than current therapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Cancer remains a leading cause of death, with current chemotherapies lacking specificity.
- Kinase inhibitors represent an advance but may have limited future benefit.
- Transcription factors control gene expression and cell behavior, often aberrantly activated in cancer.
Purpose of the Study:
- To explore transcription factors as novel therapeutic targets for cancer treatment.
- To evaluate the potential of targeting transcription factors for more effective and less toxic cancer therapies.
Main Methods:
- Analysis of transcription factor roles in cancer cell proliferation and survival.
- Review of existing and potential strategies for targeting transcription factors therapeutically.
Main Results:
- Transcription factors are frequently "on" in cancer cells, driving uncontrolled growth.
- Inactivating transcription factors can halt cancer cell growth or induce cell death.
- Normal cells exhibit redundancy, tolerating transcription factor dysfunction better than cancer cells.
Conclusions:
- Targeting transcription factors presents a promising strategy for developing novel cancer treatments.
- This approach may lead to more effective therapies with reduced toxicity compared to current options.
- Overcoming challenges in drug development for transcription factors is crucial for realizing their therapeutic potential.
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