fbpx Skip to main content
Category

Research

Using our Immune Systems to Cure Cancer

By Chris Porter, MD
Pediatric Hematologist/Oncologist
Aflac Cancer & Blood Disorders Center of Children’s Healthcare of Atlanta

 

Researchers have learned a great deal about how the human immune system can function as physiologic superheroes – able to prevent and cure diseases, including cancer. Like particularly cunning comic book villains, some cancers devise intricate plans to weaken their superhero foes – think kryptonite to Superman. In our lab, we have been investigating how blood cancer cells evade the immune system and have discovered that the cancer cells use a molecular kryptonite, called Siglec15, to weaken the immune cells. Fortunately, there may be ways to shield our immune cells and new ways to strengthen them, which we are actively pursuing every day.

Cancers derived from blood cells, including leukemia and lymphoma, are the most common cancers in children. Thanks to research, cure rates are better than ever. But cancer remains the leading cause of illness-related death in children. Thus, there is a need for better therapies, and understanding how cancer cells behave is critical to developing better medicines.

Dr. Chris Porter

A couple of years ago, our lab found that leukemia cells depend on a protein called calcineurin to evade immune cells. In the cell, calcineurin helps control the expression of a number of other proteins. One of the proteins that calcineurin controls is a signaling molecule, IL-12. This molecule is a member of a family of signaling proteins called cytokines. Researchers have known for a long time that IL-12 very strongly stimulates immune cells to kill cancer cells. However, IL-12 has not been an effective therapy, in part because it can cause several side effects. To get around this problem, we are collaborating with scientists at Emory University and the Georgia Institute of Technology. Together we hope to develop a nanomedicine to deliver IL-12 exactly to where it needs to be, where immune cells interact with cancer cells. This will effectively give additional super-powers to help the immune cells eliminate the cancer cells.

In addition, we found that calcineurin controls the expression of Siglec15, a protein of which not much is known. Leukemia and lymphoma cells seem to make a lot of Siglec15, which we know can inhibit immune cells. In fact, children with leukemia have much higher levels of Siglec15 in their blood than healthy individuals. Now we are trying to understand how the leukemia and lymphoma cells make it and how it inhibits the immune cells. In addition, we are working with a drug company that makes a medicine that can block Siglec15, which could act as a forcefield for the immune cells.

Thus, with funding from CURE, we are making great strides in figuring out ways to strengthen and protect immune cells, which should let these superheroes destroy the villainous cancer cells.

 

 

2021 Research Grants

CURE CHILDHOOD CANCER PROUDLY ANNOUNCES MORE THAN $3 MILLION IN RESEARCH GRANTS

When CURE’s fiscal year began, we were squarely in the midst of the COVID-19 pandemic and couldn’t begin to predict how the year ahead would unfold. As circumstances became more dire for many families we serve, we quickly realized we needed to invest more funds in supporting our patients and families. At the same time, revenue was declining as the pandemic forced us to cancel events and hold others virtually. While we were confident that our priority needed to be helping families through these extraordinary times, we did not want to let up on research support. How would we be able to do it all, we wondered? Our community answered by giving generously to ensure critical research could move forward even in the pandemic.

Thanks to you, CURE is delighted to announce more than $3 million in research grants for the 2021 fiscal year!

Our research priorities are clear. First, we prioritize research that is likely to reach the bedside within five years. Second, we focus on research that will improve the outcomes for the 20% of children not surviving today’s methods of treatment. In furtherance of these goals, we continue to prioritize precision medicine and advancing the Aflac Precision Medicine Program at Children’s Healthcare of Atlanta.

Four years ago, our funding made the Aflac Precision Medicine Program a reality. The results in these four short years have been dramatic. Since its clinical introduction, genetic sequencing of tumors has provided actionable results in 78% of the patients – meaning that the information obtained through this sequencing impacted the treatment of 78% of the children in some way. What an extraordinary impact this sequencing makes. CURE’s investment of $1.8 million this year will allow the Aflac Precision Medicine Program to provide genetic sequencing for more children in addition to going deeper with the genetic testing – in other words, analyzing even more genes that may be contributing to tumor growth. CURE’s Precision Medicine grant will also enable research into racial and ethnic differences which may affect a child’s outcome. With our funds, scientists will explore and identify the immune factors that contribute to racial and ethnic differences in outcome. This exciting research will significantly impact children of all races diagnosed with cancer now and in the future.

We are again funding the training of three future pediatric oncologists through our Fellowship Program: Dr. Frank Chien, Dr. Robert Lisac (Sam Robb Fellow), and Dr. Sanyu Janardan (Connolly Family Fellow). By funding their training, we remove financial impediments and allow the fellows to focus on research and care of children fighting cancer as they begin their careers.

Your generosity allowed us to do even more than we believed possible. In addition to our precision medicine initiative and our investment in the fellows, CURE is also funding eight individual research projects aimed at solving difficult to cure cancers. Our 2020-2021 Pediatric Cancer Research Initiative includes the following studies:

Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta

Waitman Aumann, MD     
The role of SIX1 in CALM-AF10 and other t-cell leukemias

Deboray DeRyckere, PhD
Nanoparticle delivery of MRX-2843 for treatment of pediatric leukemia

Robert Castellino, MD
Identifying and targeting therapeutic vulnerabilities in DIPG

Henry Curtis, PhD
Delineating the impact of anti-Galectin-9 immunotherapy on t-cell all epigenetics and survival

Shahab Shubin, MD, PhD 
Deciphering the oncogenic potential of LIN28B in group 3 medulloblastoma

Karen Effinger, MD, MS
Evaluation of vestibular dysfunction in survivors of childhood cand adolescent cancer treated with platinum-based chemotherapies

Swati Bhasin, PhD  
Therapeutic targeting of single cell RNA Seq derived t-all blast signatures

Children’s Hospital of Philadelphia

Michael Chorny, PhD
Combination Therapy of Neuroblastoma Using Co-drug Impregnated Nanocarriers

Raegan’s Playground

Raegan lived life on her own terms. She was sweet and spunky and loved unicorns. Her parents never knew how much of a fighter she was until she had to be.

She was thriving in kindergarten when she began suffering from minor illnesses that wouldn’t go away. After shuffling back and forth to appointments and different kinds of testing, Raegan was finally diagnosed with a pediatric brain tumor called DIPG.

“To say your life can change in the blink of an eye, four letters, DIPG, completely devastated our family,” recalled Raegan’s father, Marc. “We had never heard of this disease, and what we learned broke our hearts.”

Marc and his wife, Andrea, would soon learn that DIPG is a rare brain cancer for which there is no known cure. As if that wasn’t bad enough, Raegan had the worst possible genetic mutation and was given a prognosis of 6-9 months. Both Marc and Andrea work in the medical field and began scouring the internet for information and potential clinical trials.

“We shut down everything,” said Marc. “Our entire focus became about saving Raegan’s life.”

They found three clinical trials at St. Jude’s in Memphis, but by the time they arrived, two of them had closed and the third had little information available. So they packed up and came to Children’s Healthcare of Atlanta, where there were open trials that looked promising. There they met CURE.

“When we first got admitted to the Aflac Cancer Center, we were given one of the CURE tote bags,” said Andrea. “We were going through so much right then that I was very touched to feel like someone was thinking of us.”

At the same time they were facing this monumental battle, friends and fire departments around the country began to “Rally for Raegan” by posting pictures of support and contributing to a fund meant to help with Raegan’s medical expenses.

The first clinical trial worked well for seven months. But in January 2020, Raegan began to show symptoms of progression. When they came back to Atlanta for radiation, the COVID-19 pandemic hit, and the family was forced to stay in a hotel for twelve weeks. During this time, Raegan started a new clinical trial funded by CURE. She continued this treatment for five months until her tumor again showed progression.

“This all showed us how much of a fighter Raegan was,” said Marc. “She had already lived way beyond her diagnosis, and her doctor said, ‘I can tell you what we expect, but this is Raegan we’re talking about.’”

Sweet Raegan passed away at home during a tropical storm on November 8, 2020. She outlived her original diagnosis by nearly a year. And, oh how she lived.

“Raegan never stopped smiling and laughing,” said Marc. “She turned everything into her playground. The trials we went through weren’t failures because they bought us time to be with her, and every moment was precious.”

Marc and Andrea returned to Atlanta recently to pay it forward for the support they received during Raegan’s treatment.

They wanted to pay it forward to the organizations that cared for them during Raegan’s treatment. So they split the remaining funds between CURE, the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta, and the Winship Cancer Institute where she received radiation. Despite losing Raegan, they are dedicated to advancing research that will lead to cures for children with cancer.

After their experience, Andrea shared advice for parents of newly diagnosed children.

“When your child is diagnosed, it knocks the air out of you,” she said. “Once you catch your breath, start doing your own research. There may be other options out there and new treatments on the horizon. I have no regrets. The trials gave us 18 good months, much of which we wouldn’t have had. Keep fighting every day.”

Madeline and Precision Medicine

At the age of two, Madeline’s fine motor skills were in the lower 5% range. She had more baby fat than most of her little peers, and an awkward gate when she tried to run. Her family was referred to several doctors, but never discovered the cause behind her issues.

“She fell down a lot and would cry no matter how hard the fall,” recalled her mother, Bethany. “We just thought she was sensitive, but her motor skills continued to fall behind children her age.”

Just after her third birthday, Madeline had terrible leg pain and refused to walk, so Bethany took her back to the hospital. Madeline’s blood work showed that inflammation markers were very high, so doctors ordered a total body scan. They found a football-sized mass in her abdomen that had smashed her bladder and pushed into her intestines, kidney, and liver.  A biopsy of the mass confirmed a diagnosis of neuroblastoma.

“The signs were there if we look back,” Bethany said. “Madeline wasn’t sensitive. She was probably the toughest kid around. Every one of those falls hurt her badly.”

Madeline began chemotherapy right away.  After two rounds, she was able to walk again. The chemo that proved effective at first slowly stopped working to shrink the tumor. A long surgery allowed doctors to extract 85% of what remained. Unfortunately, the tumor was too intricately woven into Madeline’s spinal column for complete removal.

Madeline was enrolled in the Aflac Precision Medicine Program (APMP) funded by CURE, and the results of her genetic testing were both interesting and useful. Madeline’s tumor had a gene mutation often associated with an aggressive form of neuroblastoma. But fortunately, the remnants of Madeline’s tumor have been stable. Knowing that Madeline has that particular genetic mutation will help doctors in the future should her tumor become active.

Another part of the APMP is the genetic predisposition program, which provides care for children who are at risk for developing cancer due to a cancer predisposition syndrome or a family history of cancer. Madeline’s younger sister, Sedona, has a known genetic disorder called hemihypertrophy. So she was referred to the genetic predisposition clinic to see if her genetic mutation was the same as Madeline’s. If a genetic link between the two was revealed, it might indicate that Sedona had a high risk of developing cancer in the future.

Although no link was found, the fact that both of their children have genetic disorders had an impact on the family as a whole.

“We’ve decided not to risk having additional biological children,” Bethany said. “If we want to grow our family in the future, there are certainly other ways to do so.”

With the mass removed from her stomach and cancer treatment behind her, Madeline is a completely different child. She loves climbing on the playground and using her body now that it works better for her. She rarely cries when she falls down, which proves she is one of the toughest four-year-old kids around.

Take the next step to support research that will help kids fighting cancer… Kids like Madeline.

DONATE

What is Precision Medicine?

In 2017, CURE made an unprecedented $4.5 million commitment to the Aflac Cancer Center of Children’s Healthcare of Atlanta to launch the Aflac Precision Medicine Program (APMP). With this award, the Aflac Cancer Center would become one of only a small handful of pediatric cancer centers nationwide able to offer this cutting-edge treatment approach to children with cancer. Lauren’s story shows how important this program has become.

An easy way to understand precision medicine is to think of it as “personalized medicine.” Although we know that every child is unique, today’s childhood cancer treatment does not take into account the genetic differences of each child. Rather, a child’s cancer is treated according to disease type. But often, children with the same type of cancer respond differently to the same treatment. A chemotherapy which is effective for some may fail altogether for others because of the genetic differences at play. That is where personalized medicine comes in.

Over the past twenty years science has made incredible leaps in discovery by finding what is referred to as genetic barcodes – our DNA and RNA. We now understand what healthy cells look like and can often find triggers or markers in a tumor where something went wrong with a gene. By locating and isolating that problem and finding chemotherapies or other treatments proven effective against the genetic problem, doctors hope to improve survival while also minimizing exposures to toxic treatments which are not likely to work.

“There are really four outcomes when we look at genetic information taken from a child’s tumor,” explains Dr. Douglas Graham, Director of the Aflac Cancer. “The first is the perfect storm – we find a target that has a drug which is known to be effective against it and that drug is approved for children. We also may find a target with a matching drug that is not approved for children and would have to petition for access. The other options are not as optimistic. We may find a target with no drug known to work against it or we may find no target at all.”

The first step in the process is getting the child’s genetic information. Since July 2018, more than 40 relapsed or high-risk patients have been enrolled in the Aflac Cancer Center’s Precision Medicine Protocol.

At CURE’s Board of Directors meeting in October 2018, Dr. Daniel Wechsler, Director of Pediatric Oncology at the Aflac Cancer Center, shared, “We have received sequencing results back so far on 36 patients. Several patients have had ambiguous diagnoses confirmed as a result of (genetic) sequencing, which has helped us choose appropriate therapeutic protocols. A couple of patient tumors have shown mutations that have directed us to specific clinical trials for targeted agents.”

Fully funded by a three-year grant from CURE Childhood Cancer, the APMP is well ahead of schedule. In this second year, thirty patients were expected to be enrolled in the program.  However, Dr. Graham and Dr. Wechsler report they have enrolled many more than that. The groundwork has now been laid for more and more children to benefit from this new area of science.

While information is the key to the program, it is also the most significant limiting factor. The sheer complexity of the human genome is overwhelming, and not many are people trained to interpret genetic data. Biological informatics is a growing field of study due to this demand, and the APMP is working with the best resources available.

Also, there are currently only a handful of pediatric cancer centers across the country which precision medicine programs and the volume of information being recorded by each is significant. Finding ways to share information is a challenge to progress. This is changing, however. Doctors from the APMP are working with Memorial Sloan Kettering in New York, Cincinnati Children’s Hospital, and other leading centers to develop collaborations and efficient ways to share data.

 

CURE Childhood Cancer remains determined that precision medicine is one of the most promising methods for improving survival rates in children. And we steadfastly believe that our children deserve the best and safest options available.

A CURE-funded Study Moves to Clinical Trial

Acute myeloid leukemia (AML) is a devastating and aggressive blood cancer that affects nearly 500 children in the United States every year. AML symptoms develop so rapidly that most children feel well just weeks before diagnosis. Despite intensive research over the last 50 years, there are still only a few drugs available to treat this disease, and the survival rate is only 50%. The treatment for AML entails extremely high, toxic doses of chemotherapy. Side effects of chemotherapy include profound impairments to immune function, cardiac toxicity which can lead to heart damage, and kidney and liver dysfunction that can cause permanent, profound disability or death. In fact, current AML drug dosages put children’s organs and immune systems under so much stress that nearly 10% of AML patients die from complications of treatment rather than the disease.

Dr. Alexandra Stevens

While we can temporarily control and improve the symptoms of AML so that it becomes undetectable in the blood, the disease returns with a vengeance in nearly 50% of children. When AML recurs, it is often resistant to the few drugs effective against it, making second remissions and cures particularly challenging. To improve survival of this aggressive cancer, it is critical that scientists identify more effective, better-tolerated drugs with fewer side effects that can be safely incorporated into existing treatment regimens.

While reviewing scientific literature, Dr. Alexandra Stevens of Texas Children’s Hospital read about an antibiotic drug called atovaquone that killed a blood cancer found in adults. In reading how the drug worked, Dr. Stevens believed it would be effective against pediatric AML cells. Dr. Stevens found this drug to be particularly attractive for several reasons:

  • It is already FDA-approved and has known dosing recommendations for pediatric patients;
  • It has no appreciably serious side effects, which makes it ideal to combine with intensive AML therapy; and
  • It is already used to prevent a type of pneumonia, known as PJP pneumonia, that children with AML are at risk of acquiring and treated for prophylactically as a matter of course. This means that incorporating atovaquone into existing AML treatment should be seamless; physicians could simply use atovaquone for PJP prevention so that children could also reap the drug’s potential anti-leukemia benefits in addition to warding off PJP pneumonia.

Dr. Stevens began conducting studies testing atovaquone on pediatric AML cells in the lab, eliciting promising results: this well-tolerated drug performed as well in petri dishes as did the toxic chemotherapy that forms the current basis of pediatric AML therapy.

In response, Dr. Stevens’ team immediately began preclinical studies to confirm that incorporating atovaquone into AML treatment regimens would be safe and effective. In two short years, the team opened a limited-institution trial to identify potential issues with co-administering atovaquone with standard, upfront AML chemotherapy.

The preclinical work was recently published, and the clinical trial has already achieved more than 70% enrollment. Importantly, the next Children’s Oncology Group trial for pediatric AML will collect data on which patients receive atovaquone for PJP prophylaxis and enable researchers to use that data to help determine whether atovaquone reduces the frequency of relapse in a real-world setting.

“Our research team looks forward to continuing their work to learn how best to harness atovaquone’s effects,” said Dr. Stevens. “With the instrumental support of CURE Childhood Cancer, we hope to improve outcomes in patients with pediatric AML.”

 

Why We’re Bullish on Precision Medicine

Could a massive leap forward for cystic fibrosis patients help children with cancer?

In 1989, a research team unlocked a valuable piece of information about a disease that affects an estimated 30,000 people in the United States. After years of study, researchers discovered the gene defect that causes cystic fibrosis (CF). That discovery launched an all-out war against the disease. Patient advocate groups funded research in academic laboratories where incremental discoveries began to unravel the basic biology of the disease.

In a CF patient, there is a malfunctioning protein that doesn’t do its job of balancing salt and water in the lungs. Over time, researchers found ways to correct the error in the protein for the most common problem. In 2019, the Food and Drug Administration approved a three-drug combination that could benefit 90% of patients who suffer from the disease. It is a modern breakthrough of science that began with a single genetic discovery.

“Finding the gene responsible for CF was a ‘needle-in-a-haystack’ problem,” said Francis Collins, the director of the National Institute of Health, and director of the team that found the needle. “But thirty years along, with many bumps along the road and so many people waiting and hoping that something like this would happen – here we are.”

How does this apply to children with cancer?

The model of discovery for this leap forward offers a compelling study into research and drug development for other diseases, including childhood cancer. To understand why, we must explore the differences between cancer in adults and children.

In adults, lifestyle-related risk factors, such as smoking, being overweight, not getting enough exercise, eating an unhealthy diet, and drinking alcohol play a major role in many types of cancer. But lifestyle factors usually take many years to influence cancer risk, and they are not thought to play much of a role in childhood cancers.

Most childhood cancers are the result of DNA changes that happen early in the child’s life, sometimes even before birth. Every time a cell divides into 2 new cells, it must copy its DNA. This process isn’t perfect, and errors sometimes occur, especially when the cells are growing quickly. The causes of DNA changes in most childhood cancers are not known but are likely to be the result of random events that sometimes happen inside a cell, without having an outside cause.

The only way to find the cause of these changes is through genetic testing (also called DNA sequencing). While the primary goal of precision medicine is to bring a therapy to a child that matches the genetic error fueling their cancer, there is also a broader use. By building a large data bank and comparing the genetic errors expressed in children across the world, scientists hope to unlock that “needle-in-a-haystack” for pediatric cancer.

Because there are many types of childhood cancers, there are many gene defects to find. To do so will take steady, ongoing research funded dollar by dollar over a period of time. The road may seem long and grueling, but we believe patience and persistence will yield significant results in the future.

In the meantime, precision medicine is already proving a worthwhile investment as doctors are able to tailor therapies to children on an individual basis. There are children who are alive today because of the findings of genetic testing and precision medicine!

But until all children diagnosed with cancer can benefit from it, there is still work to do.

Previously, the estimated life span of a cystic fibrosis patient was 44 years. For most, the recent discoveries will likely turn what was a deadly disease into a treatable condition.

Children with cancer deserve the same odds and outcomes. We believe precision medicine is the best method to make a similar drastic improvement in the survival rates. To read more about our precision medicine initiative, please click here.

Take the next step to support research that will help save kids with cancer.

Vincristine Shortage Information

LATEST NEWS

As of 10/23, Pfizer has received vincristine and made shipments to hospitals. Pfizer will work under a “controlled distribution” until they reach full recovery. This means that they will hold a buffer so that no location runs out of vincristine and no child will go without their necessary treatment.

The full recovery dates are anticipated as follows:

1 mg dose – January 2020

2 mg dose – December 2019

If you are a patient family and are told you will not get a full dose of vincristine, please contact the FDA immediately at [email protected].

We will post the COG’s webinar here as soon as it is available as well as any appropriate action steps that the childhood cancer community can take to ensure this doesn’t happen again with any drug needed by children.

Please watch this informative webinar hosted by the Coalition Against Childhood Cancer and the Alliance for Childhood Cancer and led by Dr. Peter Adamson, Chair of the Children’s Oncology Group. Dr. Adamson shared information the COG has received along with a perspective on childhood cancer drug shortages, including the current situation with vincristine. The two organizations offered this webinar so that the community could have a better understanding of the shortage, how to work with care providers, how to contact the FDA when problems arise from the shortage, and advocacy steps being taken.

The recent news about a shortage of vincristine is most alarming. This is because vincristine is the chemotherapy drug most widely used to fight pediatric cancers. It has been approved to treat children with cancer for over 50 years and is a critical component of treatment regimens for children with leukemias, lymphoma, brain tumors, bone tumors, neuroblastoma, Wilms tumor, and rhabdomyosarcoma.

Parents of children with cancer are rightfully concerned with the shortage because there is no alternative or substitute for the drug. This means that hospitals and doctors are being forced to ration the drug by lowering dosages for some patients or having them skip administration of it completely.

Drug shortages are not uncommon in the United States. But a shortage of the most commonly used chemotherapy drug for children represents a crisis. Currently, the drug has only one manufacturer in the United States, making almost all pediatric cancer patients completely dependent on their supply. Any disruption of their manufacturing process in the future could create the same situation.

CURE Childhood Cancer is a part of the Coalition Against Childhood Cancer (CAC2), who has created a working group in conjunction with the Alliance for Childhood Cancer. This group is intended to guide action through this crisis, as well as work to ensure it doesn’t reoccur. We feel it is imperative that the childhood cancer community work together as one voice to combat this issue.

Dr. Peter Adamson, Chair of the Children’s Oncology Group has responded to our concerns in this letter.

At this time, the most important call to action is solely for families affected by the shortage: Families immediately impacted should contact the Food and Drug Administration (FDA) at [email protected]. If you are not directly impacted by the shortage, please do not use this email. Use of the email for purposes of complaint or advocacy will only delay action to the parents who need access.

For the longer term, Dr. Adamson writes:

In my view, as related efforts are developed for longer term, economic policy solutions, we need to focus on solutions for today’s children with cancer. In the upcoming days and weeks, I am hopeful we can arrive at focused action items for advocacy solutions that have the goal of guaranteeing cancer drug supplies for children in the United States. Proposals that could be enacted in a reasonable time frame for today’s children that merit consideration include but are not limited to (1) establishment and maintenance of a national stockpile of key cancer drugs used for the treatment of children with cancer and (2) US government purchasing contracts that provide a guaranteed buyer and may help stabilize a fragile market.

CURE Childhood Cancer is committed to keeping you up to date on the progress of the vincristine shortage, and through our partners at CAC2, we will work to ensure all children fighting cancer have an adequate supply of necessary medication. As we learn appropriate advocacy steps, we will share them here and on Facebook and Twitter.

Lauren and Precision Medicine

When Lauren was only two years old, her parents noticed a lump in her abdomen and got the worst news imaginable. Their happy, beautiful baby was diagnosed with neuroblastoma – a pediatric cancer of the nervous system. They immediately entered a world of chemotherapy, radiation, surgery, and too many side effects to mention. But after several months, Lauren’s tumor shrunk, and she was declared cancer-free.

When her health improved, Lauren dreamed of being a cheerleader. She joined a competitive squad and even made her school team. She loved every practice, meet, and football game, and she worked very hard to be her best. At 15, she was primed for high school cheering until she began experiencing hip and leg pain that sidelined her. Being so active, a doctor suggested she had arthritis in her hips, so her first attempt at recovery was physical therapy.

The PT actually helped for a time, but the pain came back. In February 2017, an MRI revealed new lesions. Once again, neuroblastoma had invaded Lauren’s body. The cancer had spread to her bones, bone marrow, lung and pelvis. In all, the imaging indicated 28 spots that were likely active tumors.

The first four cycles of chemotherapy stabilized the tumors but didn’t shrink them. Lauren moved on to immunotherapy, which is supposed to trigger the body’s immune system to attack the cancer cells. She spent alternating weeks in the hospital for more than a year. That treatment failed also.

Doctors next tried a form of treatment called MIBG therapy.

“MIBG made me very sick and uncomfortable,” Lauren recalled. “I had to stay by myself in a room with lead walls to contain the radiation. Even when I got out, I couldn’t be around people for two weeks so I wouldn’t expose them. We thought I might glow in the dark, but I never did.”

After the treatment, Lauren’s follow-up MRI showed 18 spots remaining. That was a good reduction, but not enough. Her doctor recommended that she undergo MIBG therapy again. Lauren remembered the tough side effects she experienced the first time and didn’t want to do it, but her mother talked her into it. The second round took her disease burden down to 14 spots. Because she has already received her lifetime maximum dosage of radiation, more MIBG therapy wasn’t possible.

Lauren had run out of treatment options.

When treatment options have been exhausted, there is little hope of survival. But through CURE’s funding of the Aflac Precision Medicine Program, doctors have a new tool in their toolkit. Lauren was enrolled in the program to see if there was a genetic reason her cancer was resisting treatment. Genetic testing revealed Lauren’s tumor had a genetic mutation for which there is a drug known to be effective. Lauren was immediately enrolled in a clinical trial for lorlatinib. She was given a single pill once a day, and after only four cycles, all bone metastases and bone marrow involvement had disappeared. Incredibly, the only tumor remaining at that time showed inactive.

Of course, Lauren was ecstatic with the results. She attended Spellman College in the fall of 2019. Unfortunately, Lauren’s cancer came back during her second semester and she succumbed to the disease in February 2020. While the gene therapy didn’t lead to an ultimate cure, it did afford her an extra year of joy and happiness as she pursued her dreams.

Despite the obstacles that cancer put in her way, she had an incredibly positive and hopeful attitude. Just before she passed away, she said,

“My cancer journey has made me realize that you have to live life to the fullest and never give up!”

Take the next step to support research that will help kids fighting cancer.

DONATE

What is Precision Medicine?

In 2017, CURE made an unprecedented $4.5 million commitment to the Aflac Cancer Center of Children’s Healthcare of Atlanta to launch the Aflac Precision Medicine Program (APMP). With this award, the Aflac Cancer Center would become one of only a small handful of pediatric cancer centers nationwide able to offer this cutting-edge treatment approach to children with cancer. Lauren’s story shows how important this program has become.

An easy way to understand precision medicine is to think of it as “personalized medicine.” Although we know that every child is unique, today’s childhood cancer treatment does not take into account the genetic differences of each child. Rather, a child’s cancer is treated according to disease type. But often, children with the same type of cancer respond differently to the same treatment. A chemotherapy which is effective for some may fail altogether for others because of the genetic differences at play. That is where personalized medicine comes in.

Over the past twenty years science has made incredible leaps in discovery by finding what is referred to as genetic barcodes – our DNA and RNA. We now understand what healthy cells look like and can often find triggers or markers in a tumor where something went wrong with a gene. By locating and isolating that problem and finding chemotherapies or other treatments proven effective against the genetic problem, doctors hope to improve survival while also minimizing exposures to toxic treatments which are not likely to work.

“There are really four outcomes when we look at genetic information taken from a child’s tumor,” explains Dr. Douglas Graham, Director of the Aflac Cancer. “The first is the perfect storm – we find a target that has a drug which is known to be effective against it and that drug is approved for children. We also may find a target with a matching drug that is not approved for children and would have to petition for access. The other options are not as optimistic. We may find a target with no drug known to work against it or we may find no target at all.”

The first step in the process is getting the child’s genetic information. Since July 2018, more than 40 relapsed or high-risk patients have been enrolled in the Aflac Cancer Center’s Precision Medicine Protocol.

At CURE’s Board of Directors meeting in October 2018, Dr. Daniel Wechsler, Director of Pediatric Oncology at the Aflac Cancer Center, shared, “We have received sequencing results back so far on 36 patients. Several patients have had ambiguous diagnoses confirmed as a result of (genetic) sequencing, which has helped us choose appropriate therapeutic protocols. A couple of patient tumors have shown mutations that have directed us to specific clinical trials for targeted agents.”

Fully funded by a three-year grant from CURE Childhood Cancer, the APMP is well ahead of schedule. In this second year, thirty patients were expected to be enrolled in the program.  However, Dr. Graham and Dr. Wechsler report they have enrolled many more than that. The groundwork has now been laid for more and more children to benefit from this new area of science.

While information is the key to the program, it is also the most significant limiting factor. The sheer complexity of the human genome is overwhelming, and not many are people trained to interpret genetic data. Biological informatics is a growing field of study due to this demand, and the APMP is working with the best resources available.

Also, there are currently only a handful of pediatric cancer centers across the country which precision medicine programs and the volume of information being recorded by each is significant. Finding ways to share information is a challenge to progress. This is changing, however. Doctors from the APMP are working with Memorial Sloan Kettering in New York, Cincinnati Children’s Hospital, and other leading centers to develop collaborations and efficient ways to share data.

 

CURE Childhood Cancer remains determined that precision medicine is one of the most promising methods for improving survival rates in children. And we steadfastly believe that our children deserve the best and safest options available.

2019-2020 Research Grants

CURE CHILDHOOD CANCER PROUDLY ANNOUNCES $4.3 MILLION IN  RESEARCH GRANTS

At CURE, we believe that investment in the highest quality research is the key to achieving significant progress in the fight against childhood cancer. Our focus is two-fold: we prioritize research that will reach the bedside within five years and research which will improve the outcomes for the 20% of children not surviving today’s methods of treatment. While we continue our important work to increase survival rates, it is also imperative we increase funding into safer treatments which will not compromise the rest of a child’s life. To that end, we are proud to announce $4.3 million in research grants for CURE’s fiscal year 2019–2020.

Our funding decisions are guided by our Scientific Advisory Council, a group of doctors, scientists, and researchers who conduct a thorough review of research proposals to assess both scientific merit and alignment with CURE’s goals. This year, we selected to fund 21 of the very best proposals submitted by experts at leading institutions across the country. Precision medicine continues to be a strategic focus as we enter the third year of our $4.5 million commitment which created the Aflac Cancer Center Precision Medicine Program at Children’s Healthcare of Atlanta. This unique program has already yielded significant results – giving hope to children for whom standard treatment has failed. Finally, in an effort to ensure the best and brightest minds continue to research cures for children, we will fully fund training for three pediatric oncology fellows and are providing funding to two young investigators for their research.

“We have developed an incredible partnership with CURE in the fight against childhood cancer,” said Dr. Douglas Graham, Chief of the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta. “We are so thankful for the generous gift from CURE this year to allow us to provide direct assistance to our families, fund new research projects to search for better cancer treatments, and help us train the next generation of physicians specializing in cancer care for children. The gift from CURE will also enable us to continue to develop and expand our Cancer Precision Medicine Program to enable us to provide optimal care to our most difficult to treat cancer patients. This ongoing partnership with CURE is critical to our mission to provide world class cancer care to our pediatric cancer patients.”

Our 2019-2020 Pediatric Cancer Research Initiative includes the following studies:

Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta

Douglas Graham, MD, PhD
Aflac Cancer Center Precision Medicine Program

Robert Castellino, MD
PPM1D in High-Risk, Non-SHH, Non-WNT Medulloblastoma

Zhihong Chen, PhD
Leveraging MMR Deficiency for Effective Immunotherapy in Childhood High-Grade Glioma

Deborah DeRyckere, PhD
TAM Kinases as Mediators of Chemoresistance in AML

Lubing Gu, MD
Dual Inhibition of MDM2 and XIAP for Treatment of Childhood Cancers

Lisa Ingerski, PhD
HRQOL Outcomes During Molecularly Targeted Therapy for Brain Tumors

Christopher Porter, MD
Targeting Siglec15 for the Treatment of Childhood Cancers

Erwin Van Meir, PhD
Negative Regulation of b1-Integrin Signaling by ADGRB1 in Medulloblastoma

Muxiang Zhou, MD
MYCN Inhibition as a Precision Therapy in MYCN-amplified Neuroblastoma

Augusta University Research Institute

Daquing Wu, PhD
Novel Targeted Therapy for Metastatic Osteosarcoma

Baylor College of Medicine

Alexandra Stevens, MD
A Trial of Atovaquone with Conventional Chemotherapy for Pediatric AML (ATACC AML)

Lisa L. Wang, MD
Optimizing GD2.CAR T Cell Immunotherapeutic Strategies for Relapsed Osteosarcoma and Neuroblastoma

Joanna Yi, MD
Defining the Transcriptional Control of Pediatric AML to Find New Drugs

Children’s Hospital of Philadelphia

Frank M. Balis, MD
GD2 as a Circulating Biomarker and Clinical Trial Endpoint for Neuroblastoma

Michael Chorny, PhD
Combination Therapy of Neuroblastoma Using Co-drug Impregnated Nanocarriers

Timothy Olson, MD, PhD
Bone Marrow Niche Targets to Prevent Cancer in Shwachman Diamond Syndrome

LLS PedAL Initiative, LLC

Soheil Meshinchi, MD, PhD
PedAL Initiative

Lurie Children’s Hospital of Chicago

Oren Becher, MD
Unraveling Mechanisms of Resistance to ACVR1 Inhibitors to Treat DIPG

Memorial Sloan Kettering Cancer Center

Estibaliz Lopez Rodrigo, MD
Lung Macrophage Synergy with L-MTP-PE to Target Metastatic Osteosarcoma.

Stanford University

Maria-Grazia Roncarolo, MD
Innovative Cell Therapy for Pediatric AML

Kathleen Sakamoto, MD, PhD
Niclosamide for Relapsed/Refractory Pediatric AML

Beyond Survivorship

Many people have come to know September is National Childhood Cancer Awareness Month. But fewer realize June is National Cancer Survivors Month. We should definitely celebrate survivors! After all, the journey to survivorship is arduous, and these brave children are heroes. At CURE, we love to see cancer’s youngest warriors ring the bell at the end of treatment and walk out of the hospital, shoulders back and heads held high, ready to conquer the world.

However, life after treatment for these young survivors can be tough, and most people don’t realize the price they pay to achieve survivorship. By price, we don’t mean the financial cost, but the toll of months – sometimes years – of treatments involving toxic drugs which cause damage to organs and healthy cells at the same time they kill cancer cells.

When CURE was founded in 1975, the survival rates for children diagnosed with cancer were very low. There were few survivors. With focused and collaborative research, those rates have steadily risen to above 80%. However, as is usually the case, this statistic doesn’t tell the whole story. There’s another important statistic to note: more than 95% of childhood cancer survivors will have  significant health issues by the time they are 45 years old. For those who are poor at math, 95% is only a little shy of all of them.

From heart and lung damage to secondary cancers to serious cognitive deficiencies, childhood cancer survivors enter adulthood far differently than their peers. Some of their challenges are obvious – like managing with prosthetic limbs, wheelchairs, or canine assistants. Others, less so – such as cognitive and emotional challenges. For some, survivorship can mean  moving from the confines of treatment to a different sort of cage. It’s our responsibility, as parents, friends, and adults, to ensure we do everything we can to free these survivors from this cage.

While we continue our important work to increase survival rates, it is imperative we change our thinking and increase funding into treatments which will not compromise the rest of a child’s life. CURE’s investments in precision medicine and immunotherapies hold much promise as safer cures.

Precision medicine seeks to treat the child based on his or her own genetic makeup. By analyzing the child’s DNA, doctors can match treatment to the child more precisely and avoid toxic chemotherapies that are not needed or aren’t likely to work. Fighting cancer more precisely can lead to fewer short and long-term effects. Likewise, immunotherapies work by programming one’s own immune system rather than using toxic drugs and compounds to destroy cancer cells.

These treatments offer hope for safer cures that will one day allow every child the opportunity to reach for their dreams without a cancer diagnosis standing in their way.

To learn more about CURE’s investment in groundbreaking research and see how you can join us, please click here.

X