glioblastoma

CIRM Board Approves Funding for New Clinical Trial Targeting Brain Tumors

/ Kevin McCormack / Leave a comment

The governing Board of the California Institute for Regenerative Medicine (CIRM) has awarded almost $12 million to carry out a clinical trial targeting brain tumors.

This brings the total number of CIRM funded clinical trials to 83.  

$11,999,984 was awarded to Dr. Jana Portnow at the Beckman Research Institute of City of Hope. They are using Neural stem cells (NSCs) as a form of delivery vehicle to carry a cancer-killing virus that specifically targets brain tumor cells.

Glioblastoma is the most common malignant primary brain tumor in adults and each year about 12,000 Americans are diagnosed. The 5-year survival rate is only about 10%.

The current standard of care involves surgically removing the tumor followed by radiation, chemotherapy, and alternating electric field therapy. Despite these treatments, survival remains low.

The award to Dr. Portnow will fund a clinical trial to assess the safety and effectiveness of this stem cell-based treatment for Glioblastoma.

The Board also awarded $3,111,467 to Dr. Boris Minev of Calidi Biotherapeutics. This award is in the form of a CLIN1 grant, with the goal of completing the testing needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial in people.

This project uses donor fat-derived mesenchymal stem cells that have been loaded with oncolytic virus to target metastatic melanoma, triple negative breast cancer, and advanced head & neck squamous cell carcinoma.

“There are few options for patients with advanced solid tumor cancers such as glioblastoma, melanoma, breast cancer, and head & neck cancer,” says Maria T. Millan, M.D., President and CEO of CIRM. “Surgical resection, chemotherapy and radiation are largely  ineffective in advanced cases and survival typically is measured in months. These new awards will support novel approaches to address the unmet medical needs of patients with these devastating cancers.”

The CIRM Board also voted to approve awarding $71,949,539 to expand the CIRM Alpha Clinics Network. The current network consists of six sites and the Board approved continued funding for those and added an additional three sites. The funding is to last five years.

The goal of the Alpha Clinics award is to expand existing capacities for delivering stem cell, gene therapies and other advanced treatment to patients. They also serve as a competency hub for regenerative medicine training, clinical research, and the delivery of approved treatments.

Each applicant was required to submit a plan for Diversity, Equity and Inclusion to support and facilitate outreach and study participation by underserved and disproportionately affected populations in the clinical trials they serve.

The successful applicants are:

ApplicationProgram TitleInstitution/Principal InvestigatorAmount awarded
INFR4-13579The Stanford Alpha Stem Cell ClinicStanford University – Matthew Porteus  $7,997,246  
INFR4-13581UCSF Alpha Stem Cell ClinicU.C. San Francisco – Mark Walters  $7,994,347  
INFR4-13586A comprehensive stem cell and gene therapy clinic to
advance new therapies for a diverse patient
population in California  		Cedars-Sinai Medical Center – Michael Lewis  $7,957,966    
INFR4-13587The City of Hope Alpha Clinic: A roadmap for equitable and inclusive access to regenerative medicine therapies for all Californians  City of Hope – Leo Wang  $8,000,000
INFR4-13596Alpha Stem Cell Clinic for Northern and Central California  U.C. Davis – Mehrdad Abedi  $7,999,997  
INFR4-13685Expansion of the Alpha Stem Cell and Gene Therapy Clinic at UCLA  U.C. Los Angeles – Noah Federman  $8,000,000
INFR4-13878Alpha Clinic Network Expansion for Cell and Gene Therapies  University of Southern California – Thomas Buchanan  $7,999,983  
INFR4-13952A hub and spoke community model to equitably deliver regenerative medicine therapies to diverse populations across four California counties  U.C. Irvine – Daniela Bota  $8,000,000
INFR4-13597UC San Diego Health CIRM Alpha Stem Cell Clinic  U.C. San Diego – Catriona Jamieson  $8,000,000

The Board also unanimously, and enthusiastically, approved the election of Maria Gonzalez Bonneville to be the next Vice Chair of the Board. Ms. Bonneville, the current Vice President of Public Outreach and Board Governance at CIRM, was nominated by all four constitutional officers: the Governor, the Lieutenant Governor, the Treasurer and the Controller.

In supporting the nomination, Board member Ysabel Duron said: “I don’t think we could do better than taking on Maria Gonzalez Bonneville as the Vice Chair. She is well educated as far as CIRM goes. She has a great track record; she is empathetic and caring and will be a good steward for the taxpayers to ensure the work we do serves them well.”

In her letter to the Board applying for the position, Ms. Bonneville said: “CIRM is a unique agency with a large board and a long history. With my institutional knowledge and my understanding of CIRM’s internal workings and processes, I can serve as a resource for the new Chair. I have worked hand-in-hand with both the Chair and Vice Chair in setting agendas, prioritizing work, driving policy, and advising accordingly.  I have worked hard to build trusted relationships with all of you so that I could learn and understand what areas were of the most interest and where I could help shed light on those particular programs or initiatives. I have also worked closely with Maria Millan for the last decade, and greatly enjoy our working relationship. In short, I believe I provide a level of continuity and expertise that benefits the board and helps in times of transition.”

In accepting the position Ms. Bonneville said: “I am truly honored to be elected as the Vice Chair for the CIRM Board. I have been a part of CIRM for 11 years and am deeply committed to the mission and this new role gives me an opportunity to help support and advance that work at an exciting time in the Agency’s life. There are many challenges ahead of us but knowing the Board and the CIRM team I feel confident we will be able to meet them, and I look forward to helping us reach our goals.”

Ms. Bonneville will officially take office in January 2023.

The vote for the new Chair of CIRM will take place at the Board meeting on December 15th.

City of Hope researchers discover potential therapy to treat brain tumors

/ Yimy Villa / 2 Comments

Glioblastoma (GBM) is a common type of aggressive brain tumor that is found in adults.  Survival of this type of brain cancer is poor with just 40% survival in the first-year post diagnosis and 17% in the second year, according to the American Association of Neurological Surgeons.  This disease has taken the life of former U.S. Senator John McCain and Beau Biden, the late son of U.S. President Joe Biden.

In a CIRM supported lab that conducted the study, Dr. Yanhong Shi and her team at City of Hope, a research and treatment center for cancer, have discovered a potential therapy that they have tested that has been shown to suppress GBM tumor growth and extend the lifespan of tumor-bearing mice. 

Dr. Shi and her team first started by looking at PUS7, a gene that is highly expressed in GBM tissue in comparison to normal brain tissue.  Dr. Qi Cui, a scientist in Dr. Shi’s team and the first author of the study, analyzed various databases and found that high levels of PUS7 have also been associated with worse survival in GBM patients.  The team then studied different glioblastoma stem cells (GSCs), which play a vital role in brain tumor growth, and found that shutting off the PUS7 gene prevented GSC growth and self-renewal. 

The City of Hope team then transplanted two kinds of GSCs, some with the PUS7 gene and some with the PUS7 gene turned off, into immunodeficient mice.  What they found was that the mice implanted with the PUS7-lacking GSCs had less tumor growth and survived longer compared to the mice with the control GSCs that had PUS7 gene.

The team then proceeded to look for an inhibitor of PUS7 from a database of thousands of different compounds and drugs approved by the Food and Drug Administration (FDA).  After identifying a promising compound, the researchers tested the potential therapy in mice implanted with GSCs with the PUS7 gene.  What they found was remarkable.  The therapy inhibited the growth of brain tumors in the mice and their survival was significantly prolonged.

“This is one of the most important studies in my lab in recent years and the first paper to show a causal link between PUS7-mediated modification and cancer in general and GBM in particular” says Dr. Shi.  “It will be a milestone study for RNA modification in cancer.”

The full study was published in Nature Cancer.

Dr. Shi has previously worked on several CIRM-funded research projects, such as looking at a potential link between COVID-19 and a gene for Alzheimer’s as well as the development of a therapy for Canavan disease.

Latest CIRM TRAN1 awards focus on CAR-based cell therapy to treat cancer

/ Yimy Villa / Leave a comment

Earlier this week the CIRM ICOC Board awarded $14.5 million to fund three translational stage research projects (TRAN1), whose goal is to support early development activities necessary for advancement to a clinical study or broad end use of a potential therapy. Although all three projects have their distinct area of focus, they all utilize CAR-based cell therapy to treat a certain type of cancer. This approach involves obtaining T cells, which are an immune system cell that can destroy foreign or abnormal cells, and modifying them with a chimeric antigen receptor (CAR). This enables the newly created CAR-engineered cells to identify specific tumor signals and destroy the cancer. In the sections below we will take a deeper look at each one of these recently approved projects.

TRAN1-12245

Image Description: Hideho Okada, M.D., Ph.D.

$2,663,144 was awarded to the University of California, San Francisco (UCSF) to develop specialized CAR-T cells that are able to recognize and destroy tumor cells in glioblastoma, an aggressive type of cancer that occurs in the brain and spinal cord. The specialized CAR-T cells have been created such that they are able to detect two specific signals expressed in glioblastoma. Hideho Okada, M.D., Ph.D. and his team at UCSF will test the therapy in mice with human glioblastoma grafts. They will be looking at preclinical safety and if the CAR-T cell therapy is able to produce a desired or intended result.

TRAN1-12250

Image Description: Lili Yang, Ph.D.

$5,949,651 was awarded to the University of California, Los Angeles (UCLA) to develop specialized CAR-engineered cells from human blood stem cells to treat multiple myeloma, a type of blood cancer. Lili Yang, Ph.D. and her team have developed a method using human blood stem cells to create invariant natural killer T (iNKT) cells, a special kind of T cell with unique features that can more effectively attack tumor cells using multiple mechanisms and migrate to and infiltrate tumor sites. After being modified with CAR, the newly created CAR-iNKT cells are able to target a specific signal present in multiple myeloma. The team will test the therapy in mice with human multiple myeloma. They will be looking at preclinical safety and if the CAR-iNKT cells are able to produce a desired or intended result.

TRAN1-12258

Image Description: Cristina Puig-Saus, Ph.D.

Another $5,904,462 was awarded to UCLA to develop specialized CAR-T cells to treat melanoma, a form of skin cancer. Cristina Puig-Saus, Ph.D. and her team will use naïve/memory progenitor T cells (TNM), a subset of T cells enriched with stem cells and memory T cells, an immune cell that remains long after an infection has been eliminated. After modification with CAR, the newly created CAR-TNM cells will target a specific signal present in melanoma. The team will test the therapy in mice with human melanoma. They will be looking at preclinical safety and if the CAR-TNM cells are able to produce a desired or intended result.

Scientists develop faster, smarter way to classify tumors using single-cell technology

/ Kevin McCormack / Leave a comment
Dr. Stephen Lin, CIRM Senior Science Officer

By Dr. Stephen Lin

Single-cell.  It is the new buzzword in biology.  Single-cell biology refers to the in-depth characterization of individual cells in an organ or similar microenvironment.  Every organ, like the brain or heart, is composed of thousands to millions of cells.  Single-cell biology breaks those organs down into their individual cell components to study the diversity within those cells.  For example, the heart is composed of cardiomyocytes, but within that bulk population of cardiomyocytes there are specialized cardiomyocytes for the different chambers of the heart and others that control beating, plus others not even known yet.  Single-cell studies characterize cell-to-cell variability in the body down to this level of detail to gain knowledge of tissues in a way that was not possible before.   

The majority of single-cell studies are based on next generation sequencing technologies of genetic material such as DNA or RNA.  The cost of sequencing each base of DNA or RNA has dropped precipitously since the first human genome was published in 2000, often compared to the trend seen with Moore’s Law in computing.  As a result it is now possible to sequence every gene that is expressed in an individual cell, called the transcriptome, for thousands and thousands of cells.   

The explosion of data coming from these technologies requires new approaches to study and analyze the information.  The scale of the genetic sequences that can be generated is so big that it is often not possible anymore for scientists to interpret the data manually as had been traditionally done.  To apply this exciting field to stem cell research and therapies, CIRM funded the Genomics Initiative which created the Centers of Excellence in Stem Cell Genomics (CESCG).  The goal of the CESCG is to create novel genomic information and create new bioinformatics tools (i.e. computer software) specifically for stem cell research, some of which was highlighted in past blogs.  Some of the earliest single-cell gene expression atlases of the human body were created under the CESCG. 

The latest study from CESCG investigators creates both new information and new tools for single-cell genomics.  In work funded by the Genomics Initiative, Stephen Quake and colleagues at Stanford University and the Chan-Zuckerberg Biohub studied tumor formation using single-cell approaches.  Drawing from one of the earliest published single-cell studies, the team had surveyed human brain transcriptome diversity that included samples from the brain cancer, glioblastoma. 

Recognizing that the data coming from these studies would eventually become too large and numerous to classify all of the cell types by hand, they created a new bioinformatics tool called Northstar to apply artificial intelligence to automatically classify cell types generated by single-cell studies.  The cell classifications generated by Northstar were similar to the original classifications created manually several years ago including the identification of specific cancerous cells. 

Some of the features that make Northstar a powerful bioinformatics tool for these studies are that the software is scalable for large numbers of cells, it performs the computations to classify cells very fast, and it requires relatively low computer processing power to go through literally millions of data points. 

The scalability of the tool was demonstrated on the Tabula Muris data collection, a single-cell compendium of 20 mouse organs with over 200,000 cells of data.  Finally, Northstar was used to classify the tumors from new single-cell data generated by the CESCG via samples of 11 patient pancreatic cancer patients obtained from Stanford Hospital.  Northstar correctly found the origins of cancerous cells from the specific diagnoses of pancreatic cancer that the patients had, for example cancerous cells in the endocrine cell lineage from a patient diagnosed with neuroendocrine pancreas cancer.  Furthermore, Northstar identified previously unknown origins of cancerous cell clusters from other patients with pancreatic cancer.  These new computational tools demonstrate how big data from genomic studies can become important contributors to personalized medicine.

The full study was published in Nature.

Charting a new course for stem cell research

/ Kevin McCormack / 1 Comment

What are the latest advances in stem cell research targeting cancer? Can stem cells help people battling COVID-19 or even help develop a vaccine to stop the virus? What are researchers and the scientific community doing to help address the unmet medical needs of underserved communities? Those are just a few of the topics being discussed at the Annual CIRM Alpha Stem Cell Clinic Network Symposium on Thursday, October 8th from 9am to 1.30pm PDT.

Like pretty nearly everything these days the symposium is going to be a virtual event, so you can watch it from the comfort of your own home on a phone or laptop. And it’s free.

The CIRM Alpha Clinics are a network of leading medical centers here in California. They specialize in delivering stem cell and gene therapies to patients. So, while many conferences look at the promise of stem cell therapies, here we deal with the reality; what’s in the clinic, what’s working, what do we need to do to help get these therapies to patients in need?

It’s a relatively short meeting, with short presentations, but that doesn’t mean it will be short on content. Some of the best stem cell researchers in the U.S. are taking part so you’ll learn an awful lot in a short time.

We’ll hear what’s being done to find therapies for

  • Rare diseases that affect children
  • Type 1 diabetes
  • HIV/AIDS
  • Glioblastoma
  • Multiple myeloma

We’ll discuss how to create a patient navigation system that can address social and economic determinants that impact patient participation? And we’ll look at ways that the Alpha Clinic Network can partner with community care givers around California to increase patient access to the latest therapies.

It’s going to be a fascinating day. And did I mention it’s free!

All you have to do is go to this Eventbrite page to register.

And feel free to share this with your family, friends or anyone you think might be interested.

We look forward to seeing you there.

New CAR-T cell therapy using scorpion venom developed to treat brain tumors

/ Yimy Villa / Leave a comment
Contributed by Wikimedia Commons (Public Domain)

Glioblastoma (GBM) is an aggressive form of cancer that begins in the brain and results in tumors that can be very difficult to treat. This condition has claimed the lives of Beau Biden, former Vice President Joe Biden’s son, and John McCain, former Senator of Arizona. However, a new approach to combat this condition is being developed at City of Hope and has just received approval from the FDA to conduct clinical trials. The innovative approach involves using a combination of chimeric antigen receptor (CAR)-T cell therapy and specific components of scorpion venom!

Before we dive into how the scorpion venom is being used, what exactly is CAR-T cell therapy?

Diagram of CAR-T Cell Therapy
Image Source: National Cancer Institute

This approach consists of using T cells, which are an immune system cell that can destroy foreign or abnormal cells, and modifying them with a protein called a chimeric antigen receptor (CAR). These newly designed CAR-T cells are able to identify and destroy cancer cells by detecting a specific protein on these cells. What makes CAR-T cell even more promising is that the specific protein detected can be set to virtually anything.

This is where the scorpion venom comes into play. One of the components of this venom is called chlorotoxin (CLTX), which has the ability to specifically bind to brain tumor cells.

Michael Barish, Ph.D. (Left), Christine Brown, Ph.D. (Center), Dongrui Wang (Right)
Photo Credit: Business Wire

For this study, Dr. Christine Brown, Dr. Michael Barish, and a team of researchers at City of Hope designed CAR-T cells using chlorotoxin in order to specifically detect and destory brain tumor cells. Now referred to as CLTX-CAR-T cells, they found that these newly engineered cells were highly effective at selectively killing brain tumor cells in animal models. What’s more remarkable is that the CLTX-CAR-T cells ignored non-tumor cells in the brain and other organs.

In a press release, Dr. Barish describes the CLTX-CAR-T cell approach in more detail.

“Much like a scorpion uses toxin components of its venom to target and kill its prey, we’re using chlorotoxin to direct the T cells to target the tumor cells with the added advantage that the CLTX-CAR T cells are mobile and actively surveilling the brain looking for appropriate target. We are not actually injecting a toxin, but exploiting CLTX’s binding properties in the design of the CAR. The idea was to develop a CAR that would target T cells to a wider variety of GBM tumor cells than the other antibody-based CARs.”

In the same press release, Dr. Brown talks about the promise of this newly developed therapy.

“Our chlorotoxin-incorporating CAR expands the populations of solid tumors potentially targeted by CAR T cell therapy, which is particularly needed for patients with cancers that are difficult to treat such as glioblastoma. This is a completely new targeting strategy for CAR T therapy with CARs incorporating a recognition structure different from other CARs.”

The first-in-human clinical trial using the CLTX-CAR T cells is now screening potential patients.

CIRM has funded a separate clinical trial conducted by Dr. Brown that also involves CAR-T cell therapy for brain tumors.

The full results of this study was published in Science Translational Medicine.

A video talking about this approach can also be found here.

Two studies identify a molecule that could be used to block Zika virus and kill cancer cells

/ Yimy Villa / 1 Comment
Dr. Tariq Rana (left) and Dr. Jeremy Rich (right) both lead independent teams at UC San Diego that identified a molecule, αvβ5 integrin, as the Zika virus’ key to getting into brain stem cells

Zika virus is caused by a virus transmitted by Aedes mosquitoes. People usually develop mild symptoms that include fever, rash, and muscle and joint pain. However, Zika virus infection during pregnancy can lead to much more serious problems. The virus causes infants to be born with microcephaly, a condition in which the brain does not develop properly, resulting in an abnormally small head. In 2015-2016, the rapid spread of the virus was observed in Latin America and the Caribbean, increasing the urgency of understanding how the virus affected brain development.

Working independently, Dr. Tariq Rana and Dr. Jeremy Rich from UC San Diego identified the same molecule, αvβ5 integrin, as the Zika virus’ key to entering brain stem cells. The two studies, with the aid of CIRM funding, discovered how to take advantage of the molecule in order to block the Zika virus from infecting cells. In addition to this, they were able to turn it into something useful: a way to destroy brain cancer stem cells.

In the first study, Dr. Rana and his team used CRISPR gene editing on brain cancer stem cells to delete individual genes, which was done to see which genes are required for the Zika virus to enter the cells. They discovered that the gene responsible for αvβ5 integrin also enabled the Zika virus.

In a press release by UC San Diego, Dr. Rana elaborates on the importance of his findings.

“…we found Zika uses αvβ5, which is unique. When we further examined αvβ5 expression in brain, it made perfect sense because αvβ5 is the only integrin member enriched in neural stem cells, which Zika preferentially infects. Therefore, we believe that αvβ5 is the key contributor to Zika’s ability to infect brain cells.”

In the second study, Dr. Rich and his team use an antibody to block αvβ5 integrin and found that it prevented the virus from infecting brain cancer stem cells and normal brain stem cells. The team then went on to block αvβ5 integrin in a mouse model for glioblastoma, an aggressive type of brain tumor, by using an antibody or deactivating the gene responsible for the molecule. Both approaches blocked Zika virus infection and allowed the treated mice to live longer than untreated mice. 

Dr. Rich then partnered with Dr. Alysson Muotri at UC San Diego to transplant glioblastoma tumors into laboratory “mini-brains” that can be used for drug discovery. The researchers discovered that Zika virus selectively eliminates glioblastoma stem cells from the mini-brains. Additionally, blocking αvβ5 integrin reversed that anti-cancer activity, further demonstrating the molecule’s crucial role in Zika virus’ ability to destroy cells.

In the same UC San Diego press release, Dr. Rich talks about how understanding Zika virus could help in treating glioblastoma.

“While we would likely need to modify the normal Zika virus to make it safer to treat brain tumors, we may also be able to take advantage of the mechanisms the virus uses to destroy cells to improve the way we treat glioblastoma.”

Dr. Rana’s full study was published in Cell Reports and Dr. Rich’s full study was published in Cell Stem Cell.

Drug used to treat multiple sclerosis may improve glioblastoma outcomes

/ Yimy Villa / Leave a comment
Dr. Jeremy Rich, UC San Diego

Glioblastoma is an aggressive form of cancer that invades brain tissue, making it extremely difficult to treat. Current therapies involving radiation and chemotherapy are effective in destroying the bulk of brain cancer cells, but they are not able to reach the brain cancer stem cells, which have the ability to grow and multiply indefinitely. These cancer stem cells enable the glioblastoma to continuously grow even after treatment, which leads to recurring tumor formation.

Dr. Jeremy Rich and his team at UC San Diego examined glioblastomas further by obtaining glioblastoma tumor samples donated by patients that underwent surgery and implanting these into mice. Dr. Rich and his team tested a combinational treatment that included a targeted cancer therapy alongside a drug named teriflunomide, which is used to treatment patients with multiple sclerosis. The research team found that this approach successfully halted the growth of glioblastoma stem cells, shrank the tumor size, and improved survival in the mice.

In order to continue replicating, glioblastoma stem cells make pyrimidine, one of the compounds that make up DNA. Dr. Rich and his team noticed that higher rates of pyrimidine were associated with poor survival rates in glioblastoma patients. Teriflunomide works by blocking an enzyme that is necessary to make pyrmidine, therefore inhibiting glioblastoma stem cell replication.

In a press release, Dr. Rich talks about the potential these findings hold by stating that,

“We’re excited about these results, especially because we’re talking about a drug that’s already known to be safe in humans.”

However, he comments on the need to evaluate this approach further by saying that,

“This laboratory model isn’t perfect — yes it uses human patient samples, yet it still lacks the context a glioblastoma would have in the human body, such as interaction with the immune system, which we know plays an important role in determining tumor growth and survival. Before this drug could become available to patients with glioblastoma, human clinical trials would be necessary to support its safety and efficacy.”

The full results to this study were published in Science Translational Medicine.

California gets first royalty check from Stem Cell Agency investments

/ Kevin McCormack / Leave a comment

COH image

CIRM recently shared in a little piece of history. The first royalty check, based on CIRM’s investment in stem cell research, was sent to the California State Treasurer’s office from City of Hope. It’s the first of what we hope will be many such checks, helping repay, not just the investment the state made in the field, but also the trust the voters of California showed when they created CIRM.

The check, for $190,345.87, was for a grant we gave City of Hope back in 2012 to develop a therapy for glioblastoma, one of the deadliest forms of brain cancer. That has led to two clinical trials and a number of offshoot inventions that were subsequently licensed to a company called Mustang Bio.

Christine Brown, who is now the principal investigator on the project, is quoted in a front page article in the San Francisco Chronicle, on the significance of the check for California:

“This is an initial payment for the recognition of the potential of this therapy. If it’s ultimately approved by the FDA as a commercial product, this could be a continued revenue source.”

In the same article, John Zaia, Director of the City of Hope Alpha Stem Cell Clinic, says this also reflects the unique nature of CIRM:

“I think this illustrates that a state agency can actually fund research in the private community and get a return on its investment. It’s something that’s not done in general by other funding agencies such as the National Institutes of Health, and this is a proof of concept that it can work.”

Maria Millan, CIRM’s President & CEO, says the amount of the payment is not the most significant part of this milestone – after all CIRM has invested more than $2.5 billion in stem cell research since 2004. She says the fact that we are starting to see a return on the investment is important and reflects some of the many benefits CIRM brings to the state.

“It’s a part of the entire picture of the return to California. In terms of what it means to the health of Californians, and access to these transformative treatments, as well as the fact that we are growing an industry.”

 

Novel approach to slowing deadly brain cancer stem cells may lead to new treatments

/ Todd Dubnicoff / 1 Comment

Glioblastoma, a form of brain cancer, is one of the most dreaded cancer diagnoses. Standard radiation and chemotherapy treatments for glioblastoma almost always prove ineffective because of the cancer’s ability to grow back. With their unlimited potential to self-renew, cancer stem cells within the brain tumor are thought to be responsible for its aggressive reoccurrence. Not surprisingly, researchers looking to develop more effective therapies are focused on trying to better understand the biology of these cancer stem cells in order to exploit their vulnerabilities.

Glioblastoma_-_MR_coronal_with_contrast

MRI image of high grade glioma brain tumor (white mass on left). Image: Wikipedia

This week, the Dartmouth-Hitchcock Medical Center reports that a research team led by Damian A. Almiron Bonnin has identified a cell signal that the brain cancer stem cells rely on to resist standard treatments and to regrow. They also showed that drugs which interrupt this signal reduced tumor growth in animal studies.

Because if its aggressive growth, the cells within the glioblastoma eventually become starved for oxygen or, in scientific lingo, they become hypoxic. The presence of hypoxia in brain tumors is actually predictive of a poor prognosis in affected patients. A protein called hypoxia-inducible factor (HIF) becomes activated in these low oxygen conditions and helps the cancer stem cells to survive and continue to grow. The research team found that HIF carries out this function by triggering a cascade of cell activity that leads to the secretion of a protein called VEGF out into the microenvironment of the tumor. As secreted VEGF spreads through the tumor, it stimulates new blood vessel growth which is key to the tumor’s survival by nourishing the tumor with oxygen and nutrients.

Adding drugs that block a cell’s ability to release proteins, led to a reduction in glioblastoma tumor growth both in petri dishes and in animal studies. With these results, published in Oncogene, Dr. Almiron Bonnin’s team is performing the necessary preclinical studies that could lead to testing this novel strategy in patients. He summed this effort in a press release:

s200_damian.almiron_bonnin

Damian Almiron Bonnin

“Being able to target the cancer stem cells within these tumors, like we did here, could potentially improve response to current chemotherapies and prevent recurrences, which would translate into an increase in patient survival rates.”