Hope for triple negative breast cancer sufferers: Scientists STOP the aggressive disease from spreading in animal tests
- Triple negative breast cancer doesn’t respond to targeted treatments, spreads further and is more likely to recur and prove fatal than other types
- Researchers at UConn Health and Jackson Laboratory for Genomic Medicine found that gene editors called ‘splicing factors’ are common in the tumors
- By blocking the defective splicing factors, they were able to stop the disease from spreading entirely in animals, petri dish tumors and cell studies
- FDA approved the first drug to treat splicing factor defects in 2016, and the researchers think the same kind of drug could fight cancer
Scientists have taken an important step that could lead to a treatment for the most dreaded form of breast cancer, new research reveals.
They found that blocking protein that edits DNA could stop triple negative breast cancer’s spread – a process called metastasis – in its tracks.
Triple negative breast cancers are the most aggressive form of the disease and come with higher risks of metastisizing, returning and proving fatal within five years.
A drug to treat breast cancer’s particular gene-editing defects may be a long way of – but the first drug to treat a defect in the same category, which drives a devastating form of muscular atrophy in children – is already on the market.
Researchers from UConn Health and the Jackson Laboratory for Genomic Medicine (JAX) say their findings suggest the high-dollar drug could be re-purposed to treat cancer and other diseases.
Triple negative breast cancer is the most aggressive form, and there are no targeted treatments. New research suggests that blocking a DNA editor called a splicing factor could stop its spread entirely (file)
An estimated 268,600 new cases of breast cancer are expected to be diagnosed in 2019 in the US.
Between 10 and 20 percent of those people will be diagnosed with triple negative breast cancer.
And those women are more likely to be young, and African American, according to the National Breast Cancer Association.
Each cancer actually has multiple subtypes, defined by the types of molecules that drive switch on their growth.
In breast cancer, there are three common receptors that may populate the surfaces of tumor cells: those that respond to estrogen, progesterone or HER-2/neu gene.
So, if a tumor is mostly covered in estrogen receptors, when estrogen is present and attaches to the receptor, the cancer is activated and can start to grow.
Depending on which kinds of receptors are identified on the tumor, oncologists will choose treatments that specifically target the fuel that powers that cancer.
But triple negative doesn’t receptors for any of those molecules, meaning none of the gold standard targeted treatments to cut off its power source work.
Chemotherapy is considered effective, but the cancer often comes back, with a vengeance.
Instructions for proteins and hormones are written in the genetic code, so they can become cancer fueling when DNA mutates.
But there are other molecules and processes involved in the process that leads to cell proliferation.
WHAT IS TRIPLE NEGATIVE BREAST CANCER?
Triple negative breast cancer is a form of the disease that does not have receptors for the hormones oestrogen or progesterone, or the protein HER2.
This makes it trickier to treat due to the tumour not responding to these hormonal or protein therapies.
Triple negative breast cancer makes up around 10-to-20 per cent of all forms of the disease.
It tends to be more aggressive than other breast tumours, with patients having a worse prognosis.
The condition is more common in those under 40 and black women.
It is diagnosed via a sample of the cancerous cells.
Symptoms are similar to other forms of breast cancer.
These can include:
- Lump or thickening in the breast
- Change in the size, shape or feel of the breast
- Dimpling of the skin
- Change in the shape of the nipple
- Rash or blood-stained discharge coming from the nipple
- Swelling in the armpit
Treatment usually involves surgery, chemo and radiotherapy.
Chemo may be given first to shrink the tumour before a patient goes under the knife.
It may also be given after the operation to prevent the disease returning.
Among them are splicing factors, which perform a sort of ‘cut and paste’ editing procedure, choosing the bit of a gene that needs to be used in a cell at any given moment to create a given protein.
‘A gene can code for a protein that causes cell death, or a protein that prevents it, depending on the editing,’ says study co-author Dr Olga Anczukow, a molecular biologist who studies breast cancer at both UConn Health and JAX.
So when these splicing editors get it wrong they can deliver incorrect instructions to cells, causing breast cancer cells to grow out of control or to travel to other parts of the body (metastisizing).
Dr Anczukow and her team wondered if targeting these bad editors instead of the receptors themselves could stop the spread and growth of triple negative breast cancer.
They did a sort of splicing factor population survey of triple negative breast cancer cells and found the tumors were dense in three particular splicing factors.
Since the tumors were especially rich in one, TRA2B, the research team decided to focus on it.
In studies of breast cancer cells, miniature triple negative breast cancer tumors in petri dishes and in mice, the team practiced blocking off this defective splicing factor.
When they did, they were impressed with the results. Whether in cells, petri dish tumors or animals, blocking TRA2B completely prevented the breast cancers from metastisizing.
There’s not yet a drug that can be used in humans to do the same thing. But there’s a model that might help doctors create such a drug more quickly.
In 2016, the Food and Drug Administration approved Spinraza to treat spinal muscular atrophy, a rare childhood muscle wasting disease.
Spinraza works by fixing defects in splicing factors, and the authors of the new study hope that their study’s findings mean a drug in its same ilk could be made to treat cancer as well.
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