Scientists create a drug that destroys deadly brain tumors.
Story by Talker News • 16m ago
By Mark Waghorn via SWNS
Drug that destroys the deadliest brain tumors is developed by scientists (msn.com)
A drug that destroys the deadliest brain tumors has been developed by scientists.
It passes through the blood-brain barrier that protects neurons from foreign invaders – wiping out cancerous cells. Experiments found the small molecule killed them all –
leaving healthy tissue alone.
Results were described as “very promising.”
The mice were cured – with no relapse after more than six months.
It works in combination with chemotherapy.
Tumors quickly returned in peers given only the latter and spread rapidly.
Improved therapies are urgently needed for glioblastomas – which are often incurable.
The international team believes it could be introduced in clinical practice within 5 years.
The breakthrough has potential implications for other aggressive cancers.
Leif Eriksson | University of Gothenburg (gu.se)
Lead author Professor Leif Eriksson, of Gothenburg University, Sweden, said:
“These are the first clear results with brain tumors that can lead to a treatment which completely avoids surgery and radiation. “We have also begun studying the use of our substance on other aggressive tumor forms like pancreatic cancer, triple-negative breast cancer and certain liver cancers.”
Approximately 14,000 cases of glioblastoma are diagnosed each year in the United States. Only about seven percent survive. Most patients succumb within two years, and few make it past five – a statistic that hasn’t improved in decades.
The drug, named Z4P, blocks a mechanism that fuels the tumor’s protein production – causing cells to die of stress. Cancer cells, especially those that form aggressive tumors,
are out of control. To manage this pressure, they hijack healthy cells.
Eriksson explained: “We have now succeeded in stopping this by inserting a specially developed molecule in the cells that inhibits one of these hijacked adaptive mechanisms
in the cancer cells. This causes the cancer to self-destruct.”
Advanced simulations on supercomputers came up with a version that got it
through the blood-brain barrier that prevents uptake of most pharmaceuticals.
“Today cancer treatment consists of surgery, radiation and chemotherapy.
Unfortunately, all cancer cells are not killed and the tumor returns.
“Once the cancer relapses the tumor cells have often spread and developed resistance.”
The technique described in iScience does not apply to other forms of brain cancer
because they develop differently. Current treatments for brain tumors often have severe side effects. None were identified in Z4P. The treated animals-maintained weight had no apparent changes in behavior and there was no sign of an impact on the liver.
Extensive lab tests on cells have shown the substance is non-toxic – even at very high doses. Eriksson and colleagues are now optimizing the treatment procedure and planning additional animal studies.
But they are confident it should be able to arrive relatively quickly into clinical treatment.
Eriksson said: “It largely depends on whether funding comes in that allows taking the different steps as smoothly as possible.
“If I’m optimistic perhaps it might take five years.
That’s a short timeframe, but at the same time glioblastomas are nearly 100 percent fatal,
so any improvement in medical care is major progress.”
Related video: Experimental Gel Kills 100% Of Brain Tumors In Trial
Source: Lead author professor Leif Eriksson, of Gothenburg University,
Major progress in curing brain tumors | University of Gothenburg (gu.se)
The post Scientists create a drug that destroys deadly brain tumors
appeared first on Talker.
Credit: Molecule image: X. Guillory, Photos from animal studies: D. Pelizzari-Raymundo.
2023-05-major-brain-tumors-blocking-functions.pdf
This molecule Z4P inhibits one of the mechanisms that regulate protein
production in a cancer cell. This inhibition causes the cancer cell to die.
Three pictures show the spread of the tumor after 20 days of treatment on mice.
Control: Untreated tumor. TMZ: Follow-up treatment solely with chemotherapy.
Combo: Combination treatment with chemotherapy and the inhibitor Z4P.
Researchers at the University of Gothenburg, working with French colleagues, have successfully developed a method able to kill the aggressive brain tumor glioblastoma.
By blocking certain functions in the cell with a docked molecule, the researchers cause
the cancer to die of stress. Cancer cells, especially those that form aggressive tumors,
are in one way or another out of control and live a very stressful existence.
To manage this stress,
The cancer cells hijack mechanisms that the healthy cells use to regulate protein production and process the surplus proteins that they create. Without these hijacked mechanisms, the cancer cell would die.
“We have now succeeded in stopping this hijacking by inserting a specially developed molecule in the cells that inhibits one of these hijacked adaptive mechanisms in the cancer cells. This causes the cancer to self-destruct,” says Leif Eriksson, professor of physical chemistry at the University of Gothenburg.
Swedish-French collaboration.
Leif Eriksson’s group has worked with a research group at INSERM in Rennes, France. Using super computers and advanced simulations, the researchers developed a version of the molecule that can also pass through the blood-brain barrier that protects brain tissue. They have presented their findings in the journal iScience.
The breakthrough applies to glioblastoma brain tumors. These make up about 45 percent of all brain tumors and around 400 Swedes are diagnosed with glioblastomas every year. For the EU as a whole, there are 19,000 cases annually.
Currently, the prognosis for malignant glioblastomas is very bad. Only a few percent survive five years after diagnosis and treatment. “Today, cancer treatment consists
of surgery, radiation and chemotherapy. Unfortunately, all cancer cells are not killed,
and the tumor returns. Once the cancer relapses, the tumor cells have often spread
and developed resistance,” Leif Eriksson.
Studying how it can be used with other cancers
Studies with the new method have shown very promising results. The researchers saw
that a combination treatment with the new substance and chemotherapy was enough to completely kill the tumors while also preventing relapse. Since the tumors were stressed
to death, all cancer cells disappeared, and in animal experiments with mice there was no cancer relapse after 200 days. In comparative experiments with just chemotherapy, the brain tumors relapsed after 100 days and grew rapidly.
“These are the first clear results with brain tumors that can lead to a treatment which completely avoids surgery and radiation. We have also begun studying the use of our substance on other aggressive tumor forms like pancreatic cancer, triple-negative breast cancer and certain lever cancers,” says Eriksson. There are other types of brain tumors that develop differently than glioblastomas. This new method does not work with these forms of cancer.
No side effects
Current treatments for brain tumors often have severe side effects.
With this new treatment, the researchers have not yet seen any side effects with the substance. The treated animals maintained weight, had no apparent changes in behavior and there was no sign of impact on the liver. While more in-depth studies are needed, extensive cell tests have shown that the substance is non-toxic for healthy cells even at very high doses.
Research on this molecule will now continue. There is still much to do, such as optimizing the treatment procedure and additional animal experiments. But Leif Eriksson hopes and believes that it should go relatively quickly to get the pharmaceutical into clinical treatment.
“It largely depends on whether funding comes in that allows taking the different
steps as smoothly as possible. If I’m optimistic, perhaps it might take five years.
That’s a short timeframe, but at the same time glioblastomas are nearly 100%
fatal, so any improvement in medical care is major progress,” says Eriksson.
About this brain cancer research news.
Author: Olof Lönnehed
Source: University of Gothenburg
Contact: Olof Lönnehed – University of Gothenburg
Image: The image is credited to Neuroscience News
Article in iScience: A novel IRE1 kinase inhibitor for adjuvant glioblastoma treatment
Original Research: Open access by Leif Eriksson et al. Science
“A novel IRE1 kinase inhibitor for adjuvant glioblastoma treatment”
Contact: Leif Eriksson, professor of physical chemistry at the Department of Chemistry and Molecular Biology at the University of Gothenburg. Phone: +46 (0)721-94 43 90, email: leif.eriksson@chem.gu.se
Abstract
A novel IRE1 kinase inhibitor for adjuvant glioblastoma treatment.
Highlights
In silico screening yields a structurally new and brain permeable IRE1 inhibitor.
Co-treatment with temozolomide prevents glioblastoma relapses in mice.
Validation of IRE1 as a therapeutic target for adjuvant treatment in glioblastoma.
Summary
Herein, we report the discovery of structurally new IRE1 inhibitors identified
through the structural exploration of its kinase domain. Characterization in vitro
and in cellular models showed they inhibit IRE1 signaling & sensitize glioblastoma
(GB) cells to the standard chemotherapeutic, temozolomide (TMZ).
Inositol-requiring enzyme 1 (IRE1) is a major mediator of the unfolded protein response (UPR), which is activated upon endoplasmic reticulum (ER) stress. Tumor cells experience ER stress due to adverse microenvironmental cues, a stress overcome by relying on IRE1 signaling as an adaptive mechanism.
Finally, we demonstrate that one of these inhibitors, Z4P, permeates the blood–brain barrier (BBB), inhibits GB growth, and prevents relapse in vivo when administered together with TMZ. The hit compound disclosed herein satisfies an unmet need for targeted, non-toxic IRE1 inhibitors and our results support the attractiveness of IRE1
as an adjuvant therapeutic target in GB. Scientists Find Chronic Pain Signal Pathways in Brain (msn.com)
Source: Major progress in curing brain tumors by blocking certain
functions in cells with a docked molecule (medicalxpress.com)
New drug that destroys deadly brain tumors could reach patients within 5 years.
More information: Diana Pelizzari-Raymundo et al, A novel IRE1 kinase inhibitor
for adjuvant glioblastoma treatment, iScience (2023). DOI: 10.1016/j.isci.2023.106687
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