-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Before: SWI/SNF allows oncogenic transcription
.
After: SWI/SNF is inactivated in oncogenic transcription
Research proves a new way to treat targeted enhancer addiction cancer
Chromatin degradation products can prevent transcription factors from causing cancer, which may become a potential treatment for more than 90% of prostate cancer
.
Although researchers have discovered several genes that cause prostate cancer, a new study published in the journal Nature reveals that the puppet owner who controls these lines——
Oncogenes or oncogenes, such as androgen receptor, FOXA1, ERG, and MYC are "threads".
The owner of the puppet is a chromatin remodeling complex called SWI/SNF, which controls the arrangement and compression of DNA , To adapt it to the nucleus
In the current study, researchers at the University of Michigan Health Roger Cancer Center proved that the SWI/SNF complex helps to obtain enhancers that oncogenes can bind to and drive downstream gene expression in cancer
.
Degrading this complex subunit will block cancer-causing genes, just like cutting the rope of a puppet owner
This discovery reveals a new way to treat prostate cancer driven by different genes, which account for more than 90% of all prostate cancers
.
In human cells, DNA is tightly wrapped around histones (collectively called chromatin)
.
This creates a physical barrier to all DNA-based processes
" This is the first demonstration in cancer that blocking the chromatin pathway can be used as a way to treat cancer
.
By compressing the chromatin surrounding these enhancer elements, transcription factors are prevented from binding to enhancer elements that promote cancer ," the author of the study Arul M.
Chinnaiyan, MD, said he is the director of the Michigan Translational Pathology Center and the Michigan Medical Pathology and Urology SP Hicks Professor
Researchers looked at several prostate cancer models that express different oncogenes
.
They found that blocking the SWI/SNF complex can slow the growth of cancer cells and induce cell death, especially in tumors driven by FOXA1 or androgen receptors
In the normal development process, the SWI/SNF complex is essential
.
"Normal cells can survive at the default level of gene transcription, but cancer cells are particularly addicted to these enhanced regions
The components of the SWI/SNF complex are mutated in many cancers, but rarely in prostate cancer
.
Prostate cancer driven by the androgen receptor or FOXA1 is more sensitive to SWI/SNF degradation products, even more sensitive than cancers with unit mutations
Chinnaiyan said: "In the absence of mutations, only oncogenic transcription factors are involved.
Prostate cancer cells are very sensitive to this degradation product, even more sensitive than lung cancer where a component of this pathway is mutated
.
By making SWI/SNF complex The substance fails, we have seen preferential activity against certain cancers, and there is no toxicity in normal cells or normal tissues
.
This bodes well for clinical studies using compounds targeting this approach
.
"
This also indicates the possibility of applying this method to other types of cancers that are addicted to oncogenic transcription factors, including some multiple myeloma and other blood cancers
.
The researchers used the SWI/SNF degradant developed by the Indian Aurigene Discovery Technology Company
.
These compounds are being developed for future clinical trials
.
The Rogel team will continue to study the biology of this complex, help develop compounds for this complex, and evaluate other types of cancer that may respond to this approach
.
For prostate cancer, they are exploring a combination therapy using SWI/SNF degradants and anti-androgen therapy in the laboratory
.
This method has not yet undergone clinical trials
.
Subject of research
cell
Article title
"Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer," Nature .
DOI: 10.
1038/s41586-021-04246-z
