The scientists have pinpointed likely ‘cells-of-origin’, the source cells that can grow into breast cancer, in women carrying a faulty BRCA2 gene who are at high risk of developing the disease.
The study also showed these cells have potential to be targeted with an existing cancer drug to delay tumor growth, in findings that may lead to future preventive treatments for the disease.
Women who inherit and carry a faulty BRCA2 gene have a substantially increased risk of developing breast cancer – approximately 70% of carriers will develop the disease over their lifetime.
These cancers often occur at a young age and can be clinically aggressive. Early screening is encouraged and some women undertake preventive breast surgery (mastectomy) to reduce their breast cancer risk.
In a milestone finding published in Nature Cell Biology, researchers have discovered the likely ‘cells-of-origin’ of cancer in BRCA2 carriers. By comparing cancer-free tissue samples from both carriers and non-carriers, they identified an aberrant population of cells that divide more quickly.
Study joint first author said this perturbed cell population was found in the majority of tissue samples from women with a faulty BRCA2 gene.
“Given they were found in most of the BRCA2 tissue samples from healthy females, we believe these may be the cells-of-origin that lead to future breast cancers in women that carry the BRCA2 mutation,” the author said.
The aberrant cells in BRCA2 tissue, a subset of breast ductal cells called luminal progenitor cells, stood out to the scientific team because they displayed altered protein production, which is critical for the correct growth and functioning of tissues in our bodies.
“These changes may also make the cells more vulnerable to certain therapies aimed at preventing or delaying breast cancer development,” said study joint first author.
Lead author said the team developed a pre-clinical BRCA2 model that showed similar alterations in the ductal cells, and targeted them with the existing cancer drug everolimus, which is approved to treat patients with relapsed breast cancer.
“Through pinpointing this vulnerability in protein production, we were able to show that pre-treatment with this drug delayed the formation of tumors in the pre-clinical model,” said the lead author.
“This raises the possibility that targeting specific aspects of protein production in this way could represent a new breast cancer prevention strategy for women with a faulty BRCA2 gene.”
The findings are an important first step towards the goal of preventative treatments for breast cancer in BRCA2-mutation carriers.
Study author said that while the findings were exciting, more work was needed before they could be applied in the clinic.
“While everolimus did delay tumor development in the lab, this drug can have side-effects, which might limit its capacity to be used as a preventative treatment," said the author.
“Our team want to further explore which specific parts of protein processing are dysregulated, and use this information to develop more selective and tolerable preventative treatments.
“There’s still a way to go, but we’re a big step closer.
“A few years ago, we identified the likely cells-of-origin for breast cancer in females carrying a fault in the BRCA1 gene, which is also associated with a high risk of developing breast cancer. That research has since led to an international breast cancer prevention study (BRCA-P).
“We hope that our new findings will now inform future treatment and prevention for women with a faulty BRCA2 gene.”
https://www.nature.com/articles/s41556-023-01315-5
Breast cancer 'cells-of-origin' in high-risk women
- 1,142 views
- Added
Latest News
Removal of excess chloride…
By newseditor
Posted 07 Jul
Intermittent fasting and br…
By newseditor
Posted 07 Jul
How antisense non-coding RN…
By newseditor
Posted 07 Jul
3D maps of diseased tissues…
By newseditor
Posted 06 Jul
How GLP-1 receptor agonists…
By newseditor
Posted 06 Jul
Other Top Stories
Role of Vitamin D in neuropsychiatric illness
Read more
Urine Test Detects Organ Transplant Rejection
Read more
Epigenetic modification of BDNF in extinction of fearful memories
Read more
Common acid reflux medications linked to increased kidney disease risk
Read more
The food smell regulates protein quality control and aging via micr…
Read more
Protocols
Pan-cancer proteogenomics c…
By newseditor
Posted 05 Jul
A systems biology-based ide…
By newseditor
Posted 05 Jul
Tongue orthotopic xenograft…
By newseditor
Posted 04 Jul
Monitoring norepinephrine r…
By newseditor
Posted 01 Jul
BicemuS: A new tool for neu…
By newseditor
Posted 26 Jun
Publications
The translocation of a chlo…
By newseditor
Posted 07 Jul
dsRNA formation leads to pr…
By newseditor
Posted 07 Jul
BACH1 inhibits senescence,…
By newseditor
Posted 07 Jul
Bone transport induces the…
By newseditor
Posted 06 Jul
Hypothalamic neuronal activ…
By newseditor
Posted 06 Jul
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar