New drug kicks the cancer stem cell addiction

Did you know that cancer stem cells have an addiction problem? This might sound bizarre, but the science checks out.

Cancer stem cells are found in many different types of cancer tumors. They have the uncanny ability to survive even the most aggressive forms of treatment. After weathering the storm, cancer stem cells are able to divide and repopulate an entire tumor and even take road trips to create tumors in other areas of the body.

How cancer stem cells are able to survive and thrive is a question that is being actively pursued by scientists who aim to develop new strategies that target these cells.

Cancer stem cells have a Wnt addiction

To understand why a cancer stem cell is so good at staying alive and creating new tumors, you need to get down to the protein signaling level, which is basically a cascade of protein interactions that begin at the cell surface and instruct certain activities inside the cell. During embryonic development, one of the signaling pathways that’s activated is the Wnt pathway. It’s responsible for keeping embryonic stem cells in a pluripotent state where they maintain the ability to become any cell type.

As embryonic stem cells mature into adult cells, Wnt signaling plays different roles. It helps stem cells differentiate or change into cells of various tissues and helps maintain the health and integrity of those tissues. Because Wnt signaling has varying functions depending on the developmental stage of the cells, it’s important for cells to properly regulate this pathway.

It turns out that cancer stem cells don’t do this. Typically cells need to receive certain biochemical signals to activate the Wnt pathway, but cancer stem cells acquire genetic mutations and evolve such that this pathway is constantly activated. They ramp up their Wnt signaling and never turn it off. This “Wnt addiction” allows them to stay alive and flourish in a cancerous stem cell state.

Kicking the Wnt Addiction

A team at the Max Delbruck Center (MDC) in Germany decided to kick this Wnt addiction and make cancer stem cells go cold turkey. They published their results in the journal Cancer Research this week.

Their strategy involved targeting proteins called transcription factors, the activators of genes, that are turned on during aberrant Wnt signaling in cancer stem cells. The transcription factor they focused on is called TCF4. In normal cells, biochemical signals are required to activate the Wnt cascade and a protein called beta-catenin, which transmits signals to transcription factors like TCF4 that then turn on genes. In cancer stem cells, this signal isn’t required because the Wnt pathway is permanently switched on leaving TCF4 free to activate genes that promote tumor cell survival and growth.

The researchers thought that if they could break up the partnership between beta-catenin and TCF4, that they might be able to block Wnt signaling and kill the life-line of the cancer stem cells. They screened a library of drugs and identified a small molecule called LF3 that was able to block the interaction between beta-catenin and TCF4.

A new drug kills that cancer stem cells. The image on the left shows beta catenin (red) in cell nuclei indicating that these are cancer stem cells. The image on the right shows that the new substance sucessfully removed beta catenin from the nuclei. Picture by Liang Fang for the MDC

Cancer stem cells express beta-catenin shown in red on the left. On the right, drug treatment blocks Wnt signaling and removes beta-catenin from the cancer stem cells. (Image: Liang Fang for the MDC)

The scientists tested the LF3 molecule in mice with tumors derived from human colon cancer stem cells. Senior author on the study, Walter Birchmeier, explained in an MDC press release:

Walter

Walter Birchmeier

“We observed a strong reduction of tumor growth. What remained of the tumors seemed to be devoid of cancer stem cells – LF3 seemed to be powerfully triggering these cells to differentiate into benign tissue. At the same time, no signaling systems other than Wnt were disturbed. All of these factors make LF3 very promising to further develop as a lead compound, aiming for therapies that target human tumors whose growth and survival depend on Wnt signaling.”

Upon further analysis, they found that LF3 prevented cancer stem cells from dividing into more stem cells and migrating to other tissues. Instead, they differentiated into non-cancerous tissues. Importantly, the drug did not negatively affect the function of healthy cells nearby. This is a logical concern as Wnt signaling is activated in healthy adult tissue, just in a different way than in stem cells.

This study offers a new angle for cancer treatment. Not only does LF3 force cancer stem cells to kick their “Wnt addiction”, it also spares healthy cells and tissues. This drug sounds like a promising option for patients who suffer from aggressive, recurring tumors caused by cancer stem cells.


 

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Using baking ingredient to create “nano” bombs and destroy cancer stem cells

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“I am not a cook”. Richard Nixon and the baking ingredient that could help win the “war on cancer”

In 1971 President Richard Nixon declared a “war on cancer” and signed the National Cancer Act into law. Forty years later we’re still waging that war, and cancer is still one of the leading causes of death. But now researchers in Ohio have unveiled a new weapon; a nanobomb that targets cancer stem cells.

In treating invasive cancers the standard weapons are chemotherapy and radiation, but cancer stem cells are somehow able to evade these and lie dormant. Eventually they emerge from hiding and multiply and spread throughout the body, leading to a recurrence of the cancer.

So researchers at The Ohio State University Comprehensive Cancer Center turned to nanoparticles to try and target them. Nanoparticles for those of who aren’t up on the latest trendy science topics (something I plead guilty to) are particles between 1 and 100 nanometers in size. Just to put it in context, that’s about one billionth of a meter. In other words, very small indeed.

In the past when scientists tried to use nanoparticles to carry anti-cancer therapies such as therapeutic RNA to the tumor, the cancer cells simply enfolded the RNA nanoparticles in a kind of compartment called an endosome, which rendered them useless.

In a news release, principal investigator Xiaoming He said their new approach helps the nanoparticles escape from the endosomes and attack the cancer:

“We believe we’ve overcome this challenge by developing nanoparticles that include ammonium bicarbonate, a small molecule that vaporizes when exposing the nanoparticles to near-infrared laser light, causing the nanoparticle and endosome to burst, releasing the therapeutic RNA.”

In the study, published in Advanced Materials,   He and his team put micro-RNA miR-34a inside the nanoparticles. This is a molecule known to lower the levels of a  protein that cancer stem cells need for survival. When the ammonium bicarbonate was hit with the near-infrared laser it caused the endosomes to burst and released the miR-34a, killing the cancer cell.

When they tested this approach in a mouse model of human prostate cancer it significantly reduced the size of the tumors.

Because near-infrared lasers penetrate to about half an inch this method could be used for tumors near the skin surface, and for deeper ones would only require a minimally invasive surgery to deliver the necessary dose of light.

Ammonium bicarbonate, the ingredient used to help the nanoparticles swell up, is used by the food industry for some baked goods such as cookies and crackers. It’s a little odd to think that something used in such tasty treats could also be potentially deadly – think about that next time you are browsing the cookie aisle at the supermarket.

 

 

 

 

 

 

 

 

Helping patient’s fight back against deadliest form of skin cancer

Caladrius Biosciences has been funded by CIRM to conduct a Phase 3 clinical trial to treat the most severe form of skin cancer: metastatic melanoma. Metastatic melanoma is a disease with no effective treatment, only around 15 percent of people with it survive five years, and every year it claims an estimated 10,000 lives in the U.S.

The CIRM/Caladrius Clinical Advisory Panel meets to chart future of clinical trial

The CIRM/Caladrius Clinical Advisory Panel meets to chart future of clinical trial

The Caladrius team has developed an innovative cancer treatment that is designed to target the cells responsible for tumor growth and spread. These are called cancer stem cells or tumor-initiating cells. Cancer stem cells can spread in the body because they have the ability to evade the body’s immune defense and survive standard anti-cancer treatments such as chemotherapy. The aim of the Caladrius treatment is to train the body’s immune system to recognize the cancer stem cells and attack them.

Attacking the cancer

The treatment process involves taking a sample of a patient’s own tumor and, in a laboratory, isolating specific cells responsible for tumor growth . Cells from the patient’s blood, called “peripheral blood monocytes,” are also collected. The mononucleocytes are responsible for helping the body’s immune system fight disease. The tumor and blood cells (after maturation into dendritic cells) are then combined and incubated so that the patient’s immune cells become trained to recognize the cancer cells.

After the incubation period, the patient’s immune cells are injected back into their body where they generate an immune response to the cancer cells. The treatment is like a vaccine because it trains the body’s immune system to recognize and rapidly attack the source of disease.

Recruiting the patients

Caladrius has already dosed the first patient in the trial (which is double blinded so no one knows if the patient got the therapy or a placebo) and hopes to recruit 250 patients altogether.

This is the first Phase 3 trial that CIRM has funded so we’re obviously excited about its potential to help people battling this deadly disease.  In a recent news release David J. Mazzo, the CEO of Caladrius echoed this excitement, with a sense of cautious optimism:

“The dosing of the first patient in this Phase 3 trial is an important milestone for our Company and the timing underscores our focus on this program and our commitment to impeccable trial execution. We are delighted by the enthusiasm and productivity of the team at Jefferson University (where the patient was dosed) and other trial sites around the country and look forward to translating that into optimized patient enrollment and a rapid completion of the Phase 3 trial.”

And that’s the key now. They have the science. They have the funding. Now they need the patients. That’s why we are all working together to help Caladrius recruit patients as quickly as possible. Because their work perfectly reflects our mission of accelerating the development of stem cell therapies for patients with unmet medical needs.

You can learn more about what the study involves and who is eligible by clicking here.

Stem cell stories that caught our eye: diabetes drug hits cancer, video stem cell tracker and quick n’ easy stem cells for fatal lung disease


The chemical structure of Metformin (Image source: WikiMedia Commons)

The chemical structure of Metformin (Image source: WikiMedia Commons)

Teaching an old drug new tricks.
One the quickest way to get a drug to market is to find one that’s already been FDA approved for other diseases. Reporting this week in Cell Metabolism, researchers from London and Madrid identified the mechanisms that enable the anti-diabetic drug, metformin, to kill pancreatic cancer stem cells (PanCSCs).

Though they make up a tiny portion of a tumor, cancer stem cells (CSCs) are thought to lie dormant most of the time. As a result, they evade chemotherapy only to later revive the tumor and cause relapse. So, the hypothesis goes, target and kill the CSCs and you’ll eradicate the cancer.

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Mitochondria – a cell’s power station (image source: WikiMedia Commons)

While most cancer cells produce their energy needs without the use of oxygen, the team found that PanCSCs use oxygen-dependent energy production that occurs in a cell structure called the mitochondria. Because metformin blocks key components of the mitochondria’s energy factory, the drug essentially shuts down power to the PanCSCs leading to cell death.

The PanCSCs still have another trick up their proverbial sleeves: some switch over to a mitochondria-independent form of energy production so the metformin becomes useless against the PanCSCs. However, by tweaking the levels of two proteins, the researchers forced the PanCSCs to only use the mitochondria for energy production, which restored metformin’s cancer-killing ways.

Pancreatic cancer has very poor survival rates with very limited treatment options. Let’s hope this work leads to alternatives for patients and their doctors.

It’s all about location, location, location. Or is it?
We’ve written numerous times at the Stem Cellar about the importance of a stem cell’s “neighborhood” for determining the cell type into which it will eventually specialize. But a study published this week in Stem Cell Reports put the role of a cell’s surroundings somewhat into question.

A research team at Drexel University in Philadelphia compared stem cells in the back of the brain – an area that interprets visual information – with stem cells in the front of the brain – an area responsible for controlling movement. A fundamental question about brain development is how these areas form very different structures. Are the stem cells in each part of the brain already programmed to take on different fates or are they blank slates which rely on protein signals in the local environment to determine the type of nerve cell they become?

To chip away at this question, the team isolated mouse stem cells from the back and the front on the brain. Each set was grown in the lab using the same nutrients and conditions. You might have guessed the stem cells would behave the same but that’s not what happened. Compared to the stem cells from the back of the brain, the front brain stem cells gave rise to smaller daughter cells that divided more slowly. This suggests these brain stem cells already have some built-in properties that set them apart.

The methods used in the study are as fascinating as the results themselves. The team developed a time-lapse cell-tracking system from scratch that, with minimal human intervention, tags individual daughter cells and analyzes their fate as they grow, move and specialize on the petri dish. In the movie below, Professor Andrew Cohen, one of the authors who helped design the web-based software, succinctly describes the work. Also this movie of the tracking system in action is stunning.

Kudos to the team for making the software and their data set open access. There’s no doubt this technology will lead to important new discoveries.

Quick and easy stem cells to fight deadly lung disease
Lung disease is the 3rd deadliest disease in the U.S. It afflicts 33 million people and accounts for one in six deaths. One of those diseases is Idiopathic Pulmonary Fibrosis (IPF), an incurable disease that causes scarring and thickening of the lungs and makes breathing more and more labored. People often succumb to the disease within 3 to 5 years of their diagnosis. Use of lung stem cells to replace and heal damaged tissue is a promising therapeutic strategy for IPF.

Red and green indicate lung stem cells within a spheroid. (Image credit: Henry et al. Stem Cells Trans Med September 2015-0062)

Red and green indicate lung stem cells within a spheroid. (Image credit: Henry et al. Stem Cells Trans Med September 2015-0062)

This week, a research team from North Carolina State University reported in Stem Cells Translational Medicine on a quick and easy method for growing large amounts of lung stem cells from healthy lung tissue. The typical process of harvesting the tissue, sorting the individual lung cells, and growing the cells on petri dishes can be costly and time-consuming.

Instead, the NCSU team grew the human lung stem cells in three dimensional spheres containing multiple cell types and allowed them to float in liquid nutrients. The lung stem cells are at the center of the sphere surrounded by support cells. This method better resembles the natural cellular environment of the stem cells compared to a flat homogenous lawn of cells in a petri dish.

When introduced intravenously into mice with IPF-like symptoms, these lung spheroids reduced lung scarring and inflammation, nearly matching the animals without IPF. And in a head-to-head comparison, the lung spheroids were more effective than fat-derived mesenchymal stem cells, another proposed cell source for treating lung disease. Alas, humans are not mice and more studies are necessary to reach the ultimate goal of treating IPF patients. But I’m excited about this team’s progress and look forward to hearing more from them.

Related Press Releases:

Bye Bye BORIS: Gene Silencing Gives Cancer Stem Cells the Boot

A popular theory behind why cancer tumors recur post treatment is the existence of cancer stem cells (CSCs). These cells have stem cell-like qualities and are stubbornly resistant to common cancer cell killing techniques such as radiation and chemotherapy. CSCs are resilient and can reproduce themselves after all other cancer cells die off, creating new tumors and causing cancer relapse.

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Cancer stem cells are resistant to typical cancer therapies and can cause tumor relapse.

The origin of CSCs and whether they exist in all types of cancers are questions that are still up for debate. However, it seems that the cancer field has come to a consensus that CSCs do exist in many forms of cancer, and that they are a prime target for the development of new cancer therapies. Researchers hope to develop combination therapies that target regular cancer cells and CSCs. Because what’s the use of treating tumors with drugs if they will just grow back because of pesky CSCs?

There are many proposed strategies for killing cancer stem cells. Some of them center around overcoming life-extending features that CSCs have evolved including the ability to avoid normal cell death processes. One promising technology for targeting CSCs is gene silencing. This technique uses tools that turn off the expression of specific genes (hence the silencing) that are causing cancer cells to survive or divide.

Two independent groups recently announced positive results from studies that use gene silencing technology to kill breast and colon cancer stem cells. These two stories are a great example of how pre-clinical biology from academia can translate into clinical research in industry.

On the Academic Side

A group from Lausanne University Hospital in Switzerland reported in PloS One that silencing the expression of a gene called BORIS prevented the growth of breast and colon CSCs.

BORIS inhibits the function of an important tumor suppressor gene called CTCF. A tumor suppressor gene acts as a stop sign and prevents normal cells from turning into cancer cells. When tumor suppressors can’t do their normal job due to rogue jay-walkers like BORIS, normal cells lose an important line of defense and can turn into cancer cells. Typically, BORIS is only expressed in germ cells during development and not in adult cells in the body. However, scientists have found that BORIS is reactivated in some cancer cells, typically in CSCs.

The PLoS study confirmed that BORIS was reactivated in both breast and colon CSCs. One hallmark of CSCs is their ability to survive in 3D culture systems by forming sphere-like structures. They then asked whether silencing BORIS expression in breast and colon CSCs would prevent the formation of spheres in culture. They found that without BORIS, CSCs could no longer form spheres and survive in suspension. They went on to show that when BORIS is silenced, expression of stem cell and CSC genes was reduced in both the breast and colon CSCs. The authors concluded that BORIS is an important gene for CSC survival and “could be a potential new CSC biomarker that could be used as a therapeutic target for cancer therapy.”

BORIS is expressed in breast cancer stem cells (red) but not in breast cancer cells (blue).

BORIS is expressed in breast cancer stem cells (red) but not in breast cancer cells (blue). (Alberti et al. 2015)

On the Industry Side

Regen BioPharma reported on Monday that it successfully used gene silencing technology to kill colon CSCs by silencing BORIS expression. Their positive results have prompted the company to improve and advance its gene-silencing techniques so that it can file an IND (investigational new drug) application for the BORIS gene silencing technology. An IND with the Food and Drug Administration is the final step to beginning a clinical trial in humans.

Regen has published previously in this area and acknowledged the recent findings published in PLoS. In a press release, Thomas Ichim, CSO of Regen said:

From 2006-2008, together with a team of scientists from the Institute of Molecular Medicine and the National Institutes of Health, we published that vaccinating against BORIS results in immune response against and tumor regression in breast cancer, melanoma, and glioma.  Subsequently, we published that gene silencing of BORIS can be utilized to selectively kill breast cancer cells. As we saw in the recent publication, the role of BORIS as an “Achilles Heel” of cancer is becoming more and more apparent.  We are currently in the process of advancing our gene-silencing based approaches, in part by leveraging lessons we are learning during dCellVax development, in order to file an IND for BORIS gene silencing technology.

 

Big Picture

the boot

Silencing BORIS gives cancer stem cells the boot. (Image source: Glassdoor.com)

The issue with chemotherapies and other cancer treatments is that tumors become resistant to them over time. Gene silencing offers an advantage over these strategies by directly targeting CSCs, which are resistant to first-line cancer treatments. By silencing genes in CSCs that are required for cancer cell survival and metastasis, scientists can target tumors at their source. For patients with aggressive or recurring cancers, BORIS gene silencing technology could be what the doctor will order to prevent future relapse or metastasis. Time will tell, but hopefully gene silencing technologies against CSCs will enter clinical trials sooner than later.


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Sonic Hedgehog provides pathway to fight blood cancers

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

For a lot of people Sonic Hedgehog is a video game. But for stem cell researcher Dr. Catriona Jamieson it is a signaling pathway in the body that offers a way to tackle and defeat some deadly blood cancers.

Dr. Jamieson – a researcher at the University of California, San Diego (UCSD) – has a paper published online today in The Lancet Haematology that highlights the safety and dosing levels for a new drug to treat a variety of blood cancers. CIRM funding helped Dr. Jamieson develop this work.

The drug targets cancer stem cells, the kind of cell that is believed to be able to lie dormant and evade anti-cancer therapies before springing back into action, causing a recurrence of the cancer. The drug coaxes the cancer stem cells out of their hiding space in the bone marrow and gets them to move into the blood stream where they can be destroyed by chemotherapy.

In a news release Dr. Jamieson says the drug – known by the catchy name of PF-04449913 – uses the sonic Hedgehog signaling pathway, an important regulator of the way we develop, to attack the cancer:

“This drug gets that unwanted house guest to leave and never come back. It’s a significant step forward in treating people with refractory or resistant myeloid leukemia, myelodysplastic syndrome and myelofibrosis. It’s a bonus that the drug can be administered as easily as an aspirin, in a single, daily oral tablet.”

The goal of this first-in-human study was to test the drug for safety; so 47 adults with blood and marrow cancer were given daily doses of the drug for up to 28 days. Those who were able to tolerate the dosage, without experiencing any serious side effects, were then given a higher dose for the next 28 days. Those who experienced problems were taken off the therapy.

Of the 47 people who started the trial in 2010, 28 experienced side effects. However, only three of those were severe. The drug showed signs of clinical activity – meaning it seemed to have an impact on the disease – in 23 people, almost half of those enrolled in the study.

Because of that initial promise it is now being tested in five different Phase 2 clinical trials. Dr. Jamieson says three of those trials are at UCSD:

“Our hope is that this drug will enable more effective treatment to begin earlier and that with earlier intervention, we can alter the course of disease and remove the need for, or improve the chances of success with, bone marrow transplantation. It’s all about reducing the burden of disease by intervening early.”

Partnering with Big Pharma to benefit patients

Our mission at CIRM is to accelerate the development of stem cell therapies for patients with unmet medical needs. One way we have been doing that is funding promising research to help it get through what’s called the “Valley of Death.” This is the time between a product or project showing promise and the time it shows that it actually works.

Many times the big pharmaceutical companies or deep pocketed investors, whose support is needed to cover the cost of clinical trials, don’t want to get involved until they see solid proof that this approach works. However, without that support the researchers can’t do the early stage clinical trials to get that proof.

The stem cell agency has been helping get these projects through this Catch 22 of medical research, giving them the support they need to get through the Valley of Death and emerge on the other side where Big Pharma is waiting, ready to take them from there.

We saw more evidence that Big Pharma is increasingly happy doing that this week with the news that the University of California, San Diego, is teaming up with GSK to develop a new approach to treating blood cancers.

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson is leading the UCSD team through her research that aims at killing the cancer stem cells that help tumors survive chemotherapy and other therapies, and then spread throughout the body again. This is work that we have helped fund.

In a story in The San Diego Union Tribune, reporter Brad Fikes says this is a big step forward:

“London-based GSK’s involvement marks a maturation of this aspect of Jamieson’s research from basic science to the early stages of discovering a drug candidate. Accelerating such research is a core purpose of CIRM, founded in 2004 to advance stem cell technology into disease therapies and diagnostics.”

The stem cell agency’s President and CEO, Dr. C. Randal Mills, is also quoted in the piece saying:

“This is great news for Dr. Jamieson and UCSD, but most importantly it is great news for patients. Academic-industry partnerships such as this bring to bear the considerable resources necessary to meaningfully confront healthcare’s biggest challenges. We have been strong supporters of Dr. Jamieson’s work for many years and I think this partnership not only reflects the progress that she has made, but just as importantly it reflects how the field as a whole has progressed.”

As the piece points out, academic researchers are very good at the science but are not always as good at turning the results of the research into a marketable product. That’s where having an industry partner helps. The companies have the experience turning promising therapies into approved treatments.

As Scott Lippman, director of the Moores Cancer Center at UCSD, said of the partnership:

“This is a wonderful example of academia-industry collaboration to accelerate drug development and clinical impact… and opens the door for cancer stem cell targeting from a completely new angle.”

With the cost of carrying out medical research and clinical trials rising it’s hard for scientists with limited funding to go it alone. That’s why these partnerships, with CIRM and industry, are so important. Working together we make it possible to speed up the development and testing of therapies, and get them to patients as quickly as possible.

Holy Guacamole! Nutrient in Avocado Kills Cancer Stem Cells

Over four billion avocados were sold last year in the U.S. and for good reason – they’re so darn delicious and good for you too (wish you could say the same for doughnuts). Often called the world’s perfect food, avocados are high in fiber and packed with vitamins. Even the fat they contain is the healthy kind that’s associated with lower cholesterol levels and healthier hearts. As if the news couldn’t get any better, research published this week now suggests that a nutrient found in avocado can kill cancer stem cells – a cell type thought to be the source of a cancer’s unlimited growth and spread.

avocado, the world's perfect food

avocado, the world’s perfect food

The study, reported in Cancer Research by a Canadian research team at the University of Waterloo, focuses on a particularly deadly form of blood cancer called acute myeloid leukemia (AML). Often striking adults over 65, AML has a poor prognosis with only 10% survival after five years for this age group.

The cancer is caused by rapid, abnormal growth of white blood cells in the bone marrow that eventually crowds out normal blood cells leading to a deterioration of vital functions of the blood like carrying oxygen to the body. Chemotherapy or bone marrow transplants are standard treatments but unfortunately, even when successful, a majority of AML patients will relapse.

Though they make up a tiny portion of the leukemia, cancer stem cells are thought to be the main culprits behind AML relapse due to their stem cell-like ability for unlimited growth. The research team identified a nutrient in avocados called avocatin B with the ability to kill AML cancer stem cells. The killing mechanism of avocatin B was pinpointed to its disruption of the mitochondria, the cell’s energy “factory”, in leukemia cells, which led to cell death. As senior author Professor Paul Spagnuolo points out in a university press release, this cancer killing property of avocatin B promises to have limited side effects:

“We’ve performed many rounds of testing to determine how this new drug works at a molecular level and confirmed that it targets [cancer] stem cells selectively, leaving healthy cells unharmed.”

Now, before you rush out to the grocery store and stock up on nothing but avocados, keep in mind this is a preliminary study in petri dishes. Extensive follow up studies will be required before testing in humans can begin. Also, it’s not clear if eating avocado or an avocado extract would be a sufficient method of delivering avocatin B to keep cancer stem cells at bay. It’s more likely that avocatin B would be purified and provided as a food nutrient drug or a so-called nutraceutical:

“Extracts are less refined. The contents of an extract can vary from plant to plant and year to year, depending on lots of factors – on the soil, the location, the amount of sunlight, the rain,” explains Spagnuolo. “Evaluating a nutraceutical as a potential clinical drug requires in-depth evaluation at the molecular level. This approach provides a clearer understanding of how the nutraceutical works, and it means we can reproduce the effects more accurately and consistently. This is critical to safely translating our lab work into a reliable drug that could be used in oncology clinics.”

I look forward to following this story in the months and years to come with the hope that families devastated by an AML diagnosis will have more treatment options.

Stem cell stories that caught our eye: Parkinson’s trial revived, aspirin kills cancer stem cells and a stem cell role in mother-child obesity

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Parkinson’s clinical trials back on track.
After nearly 20 years of being stuck on the clinical trial “bookshelf”, an international team from Cambridge, UK revived a cell therapy for Parkinson’s disease.

In an announcement picked up this week by the Genetic Literacy Project, the team reported they had treated their first patient. Specifically, fetal brain cells were injected into the brain of a man in his mid-50’s with the disease.

Neurons derived from human embryonic stem cells

A fluorescent microscopic image of numerous dopaminergic neurons (the type of neurons that are degenerated in Parkinson’s disease patients) generated from human embryonic stem cells. Image courtesy of the Xianmin Zeng lab at the Buck Institute for Age Research.

In Parkinson’s, nerve cells controlling movement die for poorly understood reasons. An accumulation of data through the 60’s and 70’s suggested transplantation of fetal brain cells into the Parkinson’s brain would replace the lost nerve cells and restore movement control. After initial promising results in the 80’s and 90’s, larger clinical trials showed no significant benefit and even led to a worsening of symptoms in some patients.

Due to these outcomes, the research community shelved the approach. Insights gained in the interim pointed to more ideal brain injection sites in order to help avoid side effects. Also, follow up on patients beyond the two-year run of those early trials suggested that positive effects of the cell therapy may not emerge for at least three to five years. So this latest trial will run longer to capture this time window.

One remaining snag for this therapeutic strategy is the limited number of available cells for each transplant. So in the meantime, scientists including some of our grantees are working hard at getting embryonic stem cell- or iPS cell-based therapies to the clinic. Since stem cells divide indefinitely, this approach could provide an off-the-shelf, limitless supply of the nerve cells. Stay tuned.

Targeting cancer stem cells with the Wonder Drug.
Aspirin: it’s the wonder drug that may turn out to be even more wonderful.

Ball and stick model of aspirin, the wonder drug: relieves pain and prevents cancer

Ball and stick model of aspirin, the wonder drug: relieves pain and prevents cancer

Famous for relieving pain and preventing heart attacks, aspirin may add breast cancer-killer to its resume. This week a cancer research team at the Kansas City (Mo.) Veteran Affairs Medical Center published experiments picked up by Eureka Alert showing a daily dose of aspirin could put the brakes on breast cancer.

The analysis attributed this anti-cancer effect to aspirin’s capacity to reduce the growth of cancer stem cells. These cells make up a tiny portion of a tumor but if chemotherapy or radiation treatment leaves any behind, it’s thought the cells’ stem cell-like ability for unlimited growth drives cancer relapse and spread (metastasis).

In the study, mice with tumors given a daily low dose of aspirin for 15 days had, on average, tumors nearly 50% smaller than the aspirin-free mice. In another set of experiments, the team showed aspirin could prevent tumors as well. Mice were given aspirin for 10 days before exposing them to cancer cells. After another 15 days, the aspirin treated animals had significantly less tumor growth compared to an untreated group.

Senior author Sushanta Banerjee stands behind these findings: he’s been taking an aspirin a day for three years but stresses that you should consult with your doctor before trying it yourself.

A stem cell link to the passing on of obesity from mom to child?
It’s been observed that children of obese moms have a high risk for obesity and diabetes. You might conclude that genetics are the culprit as well as lifestyle habits passed down from parent to child. But research published this week by researchers at the University of Colorado School of Medicine suggests another mechanism: they conclude the mere presence of the growing embryo in the uterus of an obese mother may instruct the child’s cells to take on more fat.

The team’s reasoning is based on an analysis of umbilical cord blood stem cells collected from babies born to 12 obese mothers and 12 normal weight mothers. In the lab, the stem cells were specialized into fat and muscle cells. The cells from babies of obese mothers showed increased fat accumulation and a lower production of proteins important for uptake of blood sugar (a state that could eventually tip the scales towards diabetes).

Certainly it’s a leap to link the property of cells in a dish to the eventual health of a child. But the results are intriguing enough that the researchers intend to follow the children as they get older to look for more connections between the state of the kids’ stem cells and their health profile.

One man’s story points to hope against a deadly skin cancer

One of the great privileges and pleasures of working at the stem cell agency is the chance to meet and work with some remarkable people, such as my colleagues here at CIRM and the researchers we support. But for me the most humbling, and by far the most rewarding experience, is having a chance to get to know the people we work for, the patients and patient advocates.

Norm Beegun, got stem cell therapy for metastatic melanoma

Norm Beegun, got stem cell therapy for metastatic melanoma

At our May Board meeting I got to meet a gentleman who exemplifies everything that I truly admire about the patients and patient advocates. His name is Norm Beegun. And this is his story.

Norm lives in Los Angeles. In 2002 he went to see his regular doctor, an old high school friend, who suggested that since it had been almost ten years since he’d had a chest x-ray it might be a good idea to get one. At first Norm was reluctant. He felt fine, was having no health problems and didn’t see the need. But his friend persisted and so Norm agreed. It was a decision that changed, and ultimately saved, his life.

The x-ray showed a spot on his lung. More tests were done. They confirmed it was cancer; stage IV melanoma. They did a range of other examinations to see if they could spot any signs of the cancer on his skin, any potential warnings signs that they had missed. They found nothing.

Norm underwent surgery to remove the tumor. He also tried several other approaches to destroy the cancer. None of them worked; each time the cancer returned; each time to a different location.

Then a nurse who was working with him on these treatments suggested he see someone named Dr. Robert Dillman, who was working on a new approach to treating metastatic melanoma, one involving cancer stem cells.

Norm got in touch with Dr. Dillman and learned what the treatment involved; he was intrigued and signed up. They took some cells from Norm’s tumor and processed them, turning them into a vaccine, a kind of personalized therapy that would hopefully work with Norm’s own immune system to destroy the cancer.

That was in 2004. Once a month for the next six months he was given injections of the vaccine. Unlike the other therapies he had tried this one had no side effects, no discomfort, no pain or problems. All it did was get rid of the cancer. Regular scans since then have shown no sign that the melanoma has returned. Theoretically that could be because the new therapy destroyed the standard tumor cells as well as the cancer stem cells that lead to recurrence.

Norm says when you are diagnosed with an incurable life-threatening disease, one with a 5-year survival rate of only around 15%, you will try anything; so he said it wasn’t a hard decision to take part in the clinical trial, he felt he had nothing to lose.

“I didn’t know if it would help me. I didn’t think I’d be cured. But I wanted to be a guinea pig and perhaps help others.”

When he was diagnosed his son had just won a scholarship to play football at the University of California, Berkeley. Norm says he feared he would never be able to see his son play. But thanks to cleverly scheduling surgery during the off-season and having a stem cell therapy that worked he not only saw his son play, he never missed a game.

Norm returned to Berkeley on May 21st, 2015. He came to address the CIRM Board in support of an application by a company called NeoStem (which has just changed its name to Caladrius Biosciences). This was the company that had developed the cell therapy for metastatic melanoma that Norm took.

“Talking about this is still very emotional. When I got up to talk to the CIRM Board about this therapy, and ask them to support it, I wanted to let them know my story, the story of someone who had their life saved by this treatment. Because of this I am here today. Because of this I was able to see my son play. But just talking about it left me close to tears.”

It left many others in the room close to tears as well. The CIRM Board voted to fund the NeoStem application, investing $17.7 million to help the company carry out a Phase 3 clinical trial, the last hurdle it needs to clear to prove to the Food and Drug Administration that this should be approved for use in metastatic melanoma.

Norm says he is so grateful for the extra years he has had, and he is always willing to try and support others going through what he did:

“I counsel other people diagnosed with metastatic melanoma. I feel that I want to help others, to give them a sense of hope. It is such a wonderful feeling, being able to show other people that you can survive this disease.”

When you get to meet people like Norm, how could you not love this job.