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Maylee and Precision Medicine

Maylee has always been kind, intelligent, and slightly feisty. Since her birth in Lagrange, Georgia, she has also been a picture of health. So when she got a violent stomach virus at the age of three, her mother, Kristin, knew it was more than just a bug.

“I never expected she would go through life without being sick,” Kristin said. “But I knew right away this was different and something much worse.”

Mom was right. As the emergency room staff began giving Maylee fluids, they also tested to see if she had meningitis. Those tests found something much more sinister; Maylee’s blood had leukemia cells in it. After confirming the diagnosis, her doctor sent her by ambulance to Children’s Healthcare of Atlanta where she would spend the next six weeks.

“I had such a wide range of emotions when the doctor said my baby had cancer,” Kristin recalled. “I was confused, overwhelmed, and scared. But I also had a strange peace because I felt the Lord say, ‘I created this child and I will take care of her.’”

Maylee’s chemotherapy treatments were very aggressive. Every child responds differently to treatment, and her little body had difficulty rebounding, which forced longer hospital stays. She also had a very unusual emotional response.

“Chemo made her angry,” Kristin recalled. “She understood what was going on – that the chemo led to her feeling bad – and she took it out on the doctors. So she wouldn’t tell us when she felt bad or hurt because that would mean more doctors in the room.”

Fortunately, Maylee reached remission soon and found a routine in the hospital, although her feistiness never let her totally forgive the doctors. After seven months, she finished treatment and was declared cancer-free.

Maylee and her family began to settle into a new routine of normalcy. She welcomed her second brother into the world and began school. But during the summer of 2018, she began to snore. It might seem innocuous, but Kristin’s mother’s intuition struck again because she had been told sleep apnea can be a sign of relapse. As they rode to the hospital for doctors to evaluate Maylee, Kristin began steeling herself for another fight against cancer, feeling the familiar mix of fear, faith, and comfort.

Something new awaited Maylee at the hospital, though. Since her original diagnosis and with a $4.5 million grant from CURE, the Aflac Precision Medicine Program had launched. This program allows doctors to look at the genetic makeup of a child’s cancer and then search for a treatment designed specifically to treat the genetic abnormality at issue. Once doctors confirmed her cancer had returned, they looked at the genetics of Maylee’s leukemia and found very interesting results.

The genetic testing revealed that Maylee has a gene called CEBPA, which causes her to be predisposed to developing leukemia. Strangely enough, doctors were happy to find this gene because they know it responds well to treatment. If genetic testing had been available when Maylee was originally diagnosed and this gene discovered, Maylee’s treatment would have been different. Rather than the months of chemotherapy, Maylee would have immediately received a bone marrow transplant. Thankfully CURE’s funding allowed the program to launch in 2017, in time to help Maylee when her cancer returned not to mention so many other children yet to be diagnosed.

Maylee has since had what is called an allogenic stem cell transplant and is recovering nicely. She is once again in remission and focusing on getting well.

The discoveries from her genetic testing didn’t end there, however. Doctors also found that her leukemia is familial and that her two brothers share the gene that predisposed Maylee to it. Maylee’s brothers were immediately enrolled in the new genetic predisposition clinic.

“We had many different options available to us when they found out,” explained Kristin. “We chose to monitor the boys and watch for any symptoms. There is no guarantee that they will ever have leukemia. We just need to look for things out of the norm, and since they are enrolled in the predisposition clinic, we can have bloodwork done immediately.”

Maylee has completed treatment and is home growing stronger each day. She ultimately forgave her doctors but was thrilled to leave them behind. While she gets better, Maylee dreams of a return to normal life with no more hospitals, cancer, or chemo. And as each day passes, she inches closer to lacing up her cleats and playing soccer without a care in the world besides the goalie in her way.

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. Maylee’s story shows how important this program has become in only its second year.

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.

CURE Childhood Cancer Announces over $4 million in Research Awards

CURE Childhood Cancer is increasing its impact into research that will develop effective treatments for the 20% of children not surviving current methods. In the past ten years alone, CURE has raised more than $35 million to fund cutting-edge research and provide critical support to families dealing with a cancer diagnosis. Our unwavering commitment is to find a cure for childhood cancer in our lifetime.

To that end, CURE announces funding in excess of $4 million for our fiscal year 2017-2018. This amount includes our largest grant ever – a $1.5 million award for the development of the Aflac Cancer Center Precision Medicine Program. The program, which will be led by Douglas K. Graham, M.D., Ph.D., director of the Aflac Cancer Center and professor of pediatrics at Emory University School of Medicine, envisions personalized, non-toxic and curative cancer therapy for all children.

“We are so grateful to CURE for this generous gift and their continued support of our patients and researchers as we work to develop new treatments for childhood cancer,” says Dr. Graham. “Through the systematic implementation of integrated, comprehensive tumor profiling and the development of novel strategies to identify individual tumors’ vulnerabilities, the Precision Medicine Program will provide state-of-the-art care for children with the highest risk tumors. Our hope is that we will be able to share these treatments with centers around the country as our new approaches are adopted elsewhere.”

“We are very excited to grow our long-standing relationship with the Aflac Cancer Center by fully funding the new Precision Medicine Program,” says Kristin Connor, CURE Childhood Cancer’s Executive Director. “CURE’s mission is to drive innovative childhood cancer research that will move the needle closer to therapies with fewer side effects for children with cancer and, eventually, cures. We believe bringing Precision Medicine capabilities to Atlanta is a very important step in advancing our mission.”

In addition to the Precision Medicine Program, CURE is awarding another $1.26 million to projects at the AFLAC Cancer Center and $1.3 million at centers of excellence around the country.

CURE’s full awards are as follows:

AFLAC Cancer & Blood Disorders, Emory University

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

Spencer, H. Trent  Ph.D, Manufacturing of a GMP compliant T-cell product to treat high risk neuroblastoma

Porter, Christopher C. MD, Targeting Siglee15 for the treatment of childhood leukemia

MacDonald, Tobey J. MD, Combined CSF-1R and STAT3 Inhibition as a Novel Immunotherapeutic Strategy for Medulloblastoma

Gu, Lubing MD, MDM4-TOP2A interaction as potential target for treatment of pediatric cancers (Renewal of 2016-2017 CURE funded project)

Kenney, Anna PhD/Dey, Targeting YB1 to prevent post-radiation medulloblastoma recurrence

Zhou, Muxiang M.D., Targeting MYCN mRNA for treatment of MYCN-amplified neuroblastoma of children

Van Meir, Erwin, G PhD, Investigating the tumor suppressor function of BAI3 in WNT medulloblastoma

Graham, Doug and Deborah DeRyckere, MERTK Inhibitor Combination Therapy for Treatment of AML

Thomas Cash, MD, MSc, A Phase I Study of 131I-MIBG with Dinutuximab for Relapsed/Refractory

Himalee Sabnis, MD, MSc, ENCERT: A Phase 1 Trial using Everolimus in combination with Nelarabine, Cyclophosphamide and Etoposide in Relapsed T cell Lymphoblastic Leukemia/Lymphoma

Children’s Oncology Group & Fred Hutchinson Cancer Research Center

Meshinchi, Soheil MD, PhD, Target Pediatric AML

Children’s Cancer Therapy Development Institute

Keller, Charles MD, Prediction & Validation of a Novel Drug Combination Against Anaplastic Wilms’ tumor

Dana-Farber Cancer Institute

Steven DuBois, MD MS, Phase 1 Trial of Dual PI3K/BRD4 Inhibitor for Children with Neuroblastoma

Seattle Children’s Hospital

Leslie Kean, MD, A First-in-Disease Phase II Trial of T cell Costimulation Blockade for GVHD Prevention

The Children’s Hospital of Philadelphia

Felix, Carolyn MD, Mechanism-Based Prevention of TOP2-Poison Related Leukemia

The University of Utah

Jones, Kevin B. Epigenetic Drivers of Clear Cell Sarcoma

Staggering yet Stagnant Innovation

What are the greatest innovations of the last forty years? Going back to our bicentennial – 1976, can you come up with the top scientific, technological, and medical discoveries that have impacted society? I had the opportunity to speak to a middle school class in Decatur, GA last week and posed that very question. Although they’ve only been alive for one decade, hands shot up all over the classroom and I began to field their responses:

“The Internet!”

Correct! There was no internet or social media. We talked to each other.

“Cell phones!”

I mentioned rotary phones but lacked the Pictionary skills to make them understand rotary dialing.

“Mobile devices!”

Another good answer. I explained the huge shoulder boom boxes but since they can store a thousand songs on a device the size of a quarter, it was lost on them.

“Color Television!”

No, we had color tv’s but only three channels with no cable or satellite.

Mouths dropped.

“Space travel!”

Well, a man walked on the moon in 1969 but you are right, there has been a great deal of space innovation since. We’ve even sent a rover to Mars.

“The Gyro Rocketter!”

I suppose so. I’m sorry, I don’t know what that is.

“You couldn’t know, I only invented it just now.”

A shy hand went halfway up nearby. With the others bemoaning how hard life must have been in the paleo-internet age, I called on the young man who tentatively asked:

“I don’t mean to offend you, but did you fear from dinosaurs back then?”

Thus ended the question and answer portion of the presentation.

When you think about it, the innovation of the last forty years has been staggering. Yet in some areas, it remains unbelievably stagnant. While we have made huge leaps of progress in the fight against many forms of cancer, there are still some childhood cancers that have eluded treatment advances altogether. I discovered this fact when my daughter was diagnosed with Ewing’s Sarcoma at the age of twelve. We were given a treatment protocol which I was told would have been nearly identical to what I would have been given had I gotten the same cancer at twelve. I am not quite as old as dinosaurs, but I was twelve in the 70’s and find it unbelievable that during this age of discovery, children are being left behind.

There are various factors contributing to this sad fact. Although incidence rates are increasing, childhood cancers are still classified as rare compared to adult cancers such as lung, breast, and prostate. Funding from the government and large cancer charities lean heavily toward the cancers that affect more people without taking age into consideration. Yet our children are counting on us to do better. Certainly there are good doctors and researchers working hard to uncover safer and more effective treatments, but there is still a long way to go. That is why CURE is so vitally important. We focus our funding on projects aimed at improving outcomes for the 20% of children not surviving today’s methods of treatment. In addition, we fund projects for developing therapies that will preserve a child’s quality of life after treatment.

Click here to see a list of the research projects we are currently funding and join our search for a CURE

CURE Welcomes Dr. Douglas Graham as the new Director of the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta

We are very excited to welcome Dr. Douglas Graham to the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, and introduce him to the CURE community. We enjoy a strong partnership with the Aflac Cancer Center, providing funding for promising research conducted by its researchers, annual funding of two fellows (soon to be three!), and serving patients and families – often within its four walls – cared for its the skilled doctors and nurses. We are proud of and grateful for this partnership. In the letter below, Dr. Graham shares insight and his vision for the Aflac Cancer Center. We look forward to continue to work in partnership for the good of childhood cancer patients and their families and all who care for them.

Screen Shot 2016-02-10 at 11.34.31 AMAs the recently appointed Director of the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta, it is a privilege to become a part of the CURE Childhood Cancer family. Thank you for your remarkable support which has enabled the Aflac Cancer Center to become one of the premier centers in the country for children to receive every level of cancer care.  Your financial support has been critical to our research to develop better cancer treatments, our fellowship program to train the next generation of pediatric cancer doctors and for our clinical care, which includes family emergency funds.

Kristin Connor, CURE’s Executive Director, graciously provided me with this opportunity to give you a little more insight into care and research offered by the Aflac Cancer Center, and a few exciting programs that lie ahead.

The Aflac Cancer Center has made enormous strides with support such as CURE’s, and our advances have been recognized nationally. Last year we were ranked by US News and World Report as the number one program in the state of Georgia to treat pediatric cancer patients and the number nine program in the entire country!  We now have 80 pediatric specialists who are hematology/oncology/BMT faculty, and we are one of the five largest pediatric oncology programs in the nation. This is significant because we encounter every type of childhood cancer, and we are able to provide the most sophisticated care for the sickest of children with cancer, while simultaneously being a top-rated research center.  We are a major referral center for the country, having cared for children from 43 states.

We participate nationally in the Children’s Oncology Group (COG), which is a collaborative group of cancer doctors across the country who take care of more than 90% of all children with cancer in the US. Within COG, we have been selected as one of only 21 sites (out of 223 COG member institutions) to be given access to the newest of cancer drugs in early phase clinical trials through the COG Phase I Consortium. Our goal is to continue to offer new therapies through COG as well as to move new treatment ideas into the clinic developed by our cancer physicians and researchers.  Some new research discoveries both in gene therapy and in new cancer drug development made by our faculty are the basis for new clinical trials which are planned to be launched in the coming year in brain tumors and in leukemia.

Two examples of innovative therapies we have initiated at the Aflac Cancer Center are our MIBG program for neuroblastoma and our CAR-T immunotherapy program for relapsed childhood leukemia. We are one of the few places in the country to offer MIBG therapy, and the COG is including the Aflac Cancer Center as one of the treatment sites for an upcoming MIBG clinical trial.  A new MIBG treatment room is being planned to accommodate this anticipated increase in patient referrals.

The CAR-T therapy for relapsed leukemia involves harnessing one’s own immune system to combat cancer.  In this type of therapy, immune cells (T cells) are taken from the leukemia patient and modified in cell culture to be able to seek out and kill leukemia cells. The Aflac Cancer Center is one of only a handful of centers in the country to be selected as a treatment site. This therapy is successful in offering hope to children with resistant leukemia who have no other treatment options resulting in cures not previously possible.

Thank you, again, for your remarkable support of cutting edge research to cure more kids, and for your dedication to provide family centered care for kids with cancer. I look forward to continuing our strong partnership so that we can provide the best care possible for children with cancer, both today and tomorrow.

Major Breakthrough in Fight Against Pediatric Brain Cancer; CURE Funds Clinical Trial

The Food and Drug Administration (FDA) has granted The University of Texas MD Anderson Cancer Center approval to proceed with a new pediatric cancer treatment, called the NOAH Protocol. This investigative treatment aims at reducing and eliminating several types of pediatric brain cancer.  Children with recurrent refractory brain tumors currently have no therapeutic options, and unfortunately succumb to their disease. The NOAH protocol offers new hope for groundbreaking results.

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MD Anderson Children’s Cancer Hospital is expected to begin enrolling eligible patients in the new, Phase- I clinical trial in January 2015. The NOAH Protocol stands for “New Opportunity Advancing Hope” and is designed to deliver patients’ own activated immune cells (natural killer cells) directly to the tumor area in the brain. This immunotherapeutic approach will use cutting edge technologies to promote a paradigm shift in brain tumor treatment.

The conceptualization and initiation of the study was due to the will of one mom (Amber Larkin who founded Noah’s Light Foundation) and the strength of one little boy (Noah Larkin), who fought long and hard, but unfortunately succumbed to medulloblastoma at the age of 9. They were joined very shortly thereafter by another mom (Amber Bender who founded Addis Faith Foundation) and one very little girl, Addison Bender, who lost her tenacious battle against ATRT at 2 years of age.

Propelled by these families and their foundations as well as additional research support from CURE Childhood Cancer and other organizations, a multidisciplinary team of researchers and fund-raising specialists at MD Anderson worked very hard to translate their dreams of developing novel treatment approaches for children with recurrent/refractory fourth ventricular brain tumors, into reality.  The team consists of neuro-oncologists, pediatric oncologists, immunologists/transplant physicians, neurosurgeons and basic neuroscience researchers.

More information may be found at www.clinicaltrials.gov under the identifier: NCT02271711 or through the trial Private Investigator, Dr. Soumen Khatua at skhatua@mdanderson.org.

Seeking a Kinder Cure

Dr. Robert Craig Castellino

A child can be cured of cancer and still not be well.

Roughly 80 percent of children diagnosed with medulloblastoma – the most common malignant brain tumor in children – are cured. But the treatment that typically includes surgery, chemotherapy and radiation used to kill the cancer growing in a child’s still-developing brain itself often causes life-long damage.

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“The problem with current treatments is that most of those children are pretty severely neurologically devastated afterwards. They are ‘cured’, but not really,” says Dr. Robert C. Castellino, a pediatric hematology/oncology specialist and researcher at the Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta.

Many survivors of medulloblastoma, a tumor that develops at the back of the brain, need assistance with activities of daily living such as feeding, bathing and dressing. This means that, often, there are no ballet recitals, no homerun trots at Little League baseball games.

So, when he isn’t caring for young patients, with CURE’s funding, Dr. Castellino is conducting research he hopes will lead to a gentler cure for medulloblastoma.

Dr. Castellino’s research focuses on the gene called wild-type p53-induced phosphatase — abbreviated as WIP1 and pronounced as whip one.  “In essence, what I’m trying to do is to see why WIP1 seems to cause medulloblastomas in children,” says Dr. Castellino.

WIP1 seems to disrupt the functions of another gene called TP53. The gene’s role in preventing and fighting cancer is well documented, Dr. Castellino notes.

“p53 is probably one of the most studied genes for its role in cancer prevention, and cancer development when p53 is not working properly,” Dr. Castellino says.

But for p53 to do its job, phosphates must attach to specific areas on the p53 molecule. High levels of WIP1 remove the phosphates from p53.

“A major role of p53 is to stop cancer,” says Dr. Castellino. “WIP1 stops p53 from stopping cancer.”

High levels of WIP1 promote the growth of cancer cells, Dr. Castellino says.

“My number one goal is to try to understand how that happens,” he says. “We’re also trying to understand why lots of WIP1 seems to prevent medulloblastoma cells from dying.”

To advance his research, CURE has provided Dr. Castellino with a grant which will allow him to learn more about inhibiting WIP1 in specific models of medulloblastoma, known as “Sonic Hedgehog-activated” models.

The goal is to study development of medulloblastoma  that express high levels of the WIP1 gene. The CURE grant is helping Dr. Castellino determine if inhibiting WIP1 can suppress the growth of medulloblastoma.

Castellino may also have a good lead on a treatment.

“We have at least one compound that we found seems to prevent WIP1 from working and it seems to stop the growth of cells in a test tube,” Dr. Castellino says.

Dr. Castellino has found that targeting a protein designated as Arl13b may be a more effective treatment for medullablastoma than current therapies. A second CURE grant is helping him explore this possibility.

“Once compounds are identified that stop WIP1 from working and medulloblastoma tumors from developing and growing”, Dr. Castellino says, “I think we will be one step closer to finding drugs that can cure children of medulloblastoma, while preventing bad effects which keep medulloblastoma survivors from growing up as normal, healthy children”.

 

CURE Talks with Annamarie Robb

As we reach the conclusion of the week dedicated to honoring the 5 year anniversary of the passing of Sam Robb, we wanted to share with you an interview held with Annamarie Robb, Sam’s mother. In this video Annamarie discusses how CURE Childhood Cancer supported the Robb family, how the Robb family continues to support CURE, and why it is important for CURE to continue to fund childhood cancer research.

For more information on The Sam Robb Fund please click here.

Research Initiatives Show Progress in Finding a CURE

CURE Childhood Cancer is dedicated to conquering childhood cancer through funding targeted research. Currently, we’re supporting eleven specific projects, most of which focus on finding effective treatments for the 20% of kids who do not survive.

As we wrap up the 2011-2012 year we wanted to spend some time in a series of blogs giving you a summary of the research initiatives that we helped fund throughout the year. In the past 12 months we have committed more than $1.2 million in research grants and believe it is important for all of us to understand the progress of these research initiatives.

Below is a summary of Dr. Kelly Goldsmith’s research study and the progress that it has made in the past year.

Goldsmith versus Neuroblastoma

Dr. Goldsmith is conducting a study that addresses an important area of research in the mechanisms of tumor growth and treatment resistance in high-risk neuroblastoma, which may result in improved treatment strategies. It explores several areas, including the pathway that prevents normal regulated cell death (apoptosis), that allows tumor to continue its growth; and it seeks to characterize the regulation of an important genetic pathway causing chemotherapy resistance.

Recently, the study was able to identify a protein (mcl-1) that is acting as a barrier to treatment, by promoting chemotherapy resistance. his work has shown that this protein is regulated or manged by another called EGFR, and suggests that treatments should target the regulating protein, EGFR. This has potential to improve success in treating resistance in relapsed tumors. It has also identified an important molecule, Bax, that is de-activated in these tumors, which leads to failure of apoptosis. Future work will try to characterize what causes that de-activation, and will look to ways to reverse that.

The results of this research will be published in Cancer Research and the data is expected to be used for the Department of Defense Pediatric Grant application this year.

 

 

Endocrine Problems After Childhood Cancer Treatment

Written by Brooke Cherven, RN, MPH, CPON and Lillian Meacham, MD

Survival rates for childhood cancer have grown greatly over the last few decades thanks to many advances in pediatric cancer treatment. Today the majority of children diagnosed with cancer will become long-term survivors. Survivors can be at risk for developing health problems after cancer treatment. these health problems are called late effects and can include endocrine problems.

What are Endocrine Problems?
An endocrinologist, or hormone doctor, treats diseases or health problems affected by hormones. Hormones are needed for normal growth, puberty, thyroid and adrenal gland function and to regulate glucose levels. Common hormone problems seen in childhood cancer survivors include: short stature, growth hormone deficiency, thyroid problems, problems with adrenal glands and early or late puberty. In a study of the Aflac Cancer Survivor Program the most common problems seen in survivors were endocrine. In this study almost 60% of survivors had a hormone related problem such as; poor growth, early or late puberty, low bone mineral density, thyroid problems or being over or underweight.

Who Needs to See an Endocrinologist?
Certain cancer treatments can put survivors at risk for developing endocrine problems. If your child is at risk for developing an endocrine problem because of their cancer treatment, they may see an endocrinologist during their survivor clinic visit. If your child begins to develop an endocrine problem your oncologist may send you to see an endocrinologist.

The most common treatment associated with endocrine problems is radiation to the head or brain. This can damage the pituitary gland, located in the middle of the brain. The pituitary gland regulates growth through the production of growth hormone. It also produces hormones which regulate the thyroid and adrenal gland and regulate puberty. Damage to the pituitary gland can then cause an imbalance of these hormones. Radiation of the thyroid gland or ovary or testes can also disturb hormone balance. Only a few chemotherapies alter hormone production by damaging the ovary or testes. Diabetes mellitus can occur in survivors especially those who are overweight or being treated with steroids like prednisone or decadron.

How Do I See an Endocrinologist?
There are pediatric endocrinologists in most major cities. In the Aflac Cancer Center there are 2 endocrinologists available to see hematology and oncology patients. Dr. Briana Patterson follows patients who are treated for brain tumors and Dr. Lillian Meacham sees patients in the Aflac Cancer Survivor Program and the Aflac Endocrine Clinic. Because it is likely a survivor will have an endocrine problem the survivor program has an endocrinologist available during survivor clinic. Any survivor who is at risk for developing an endocrine problem will be scheduled to see an endocrinologist during their survivor clinic visit. It is hoped that this will be more convenient for the family. Seeing the endocrinologist during survivor clinic will save an extra trip for the family and allow labs to be drawn at the same time. This also helps improve communication between the survivor and endocrine doctors and nurses.

What Will an Endocrinologist Do?
The endocrinologist will want to know about your child’s health history and will ask questions about your family history including any family members who have had endocrine problems. She will do a physical exam including height, weight and calculate your child’s Body mass index (BMI). This will determine if your child is of normal weight, underweight, overweight or obese. She will also want to know how your child is progressing through puberty and will conduct a breast exam or testicular exam. This will help identify any problems with puberty and development.

Usually the endocrinologist will order blood tests to check different hormone levels. She may also order a bone age which is an x-ray of the left hand and will show how your child’s bones are maturing.

How do you Treat Hormone Problems?
Most hormone problems can be treated by giving hormone therapy. Some therapies are pills, some are shots, some are patches and some are nasal sprays. If your child is placed on an endocrine treatment they will need regular follow up to monitor the dose of the hormone therapy. Most hormone treatments are long-term if not life-long.

To learn more about childhood cancer survivorship visit www.cancersurvivorlink.org or www.choa.org/cancersurvivorship.

Dr. Kelly Goldsmith and her Fight Against Neuroblastoma

Last year, CURE Childhood Cancer awarded more than one million dollars in new research grants to scientists at the Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta and Emory University.

One of the award recipients was Kelly Goldsmith, an MD in Pediatric Hematology/Oncology at the Aflac Cancer Center. Dr. Goldsmith is a graduate of the University of Alabama Birmingham School of Medicine and completed her residency, fellowship and early attending years at The Children’s Hospital of Philadelphia, the premier neuroblastoma research center in the country. She joined the Aflac Cancer Center in 2009, after giving a lecture as part of the center’s Research Seminar Series and meeting with the staff.

“Children’s was the perfect place and fit for me as both a physician and a scientist,” said Dr. Goldsmith.

“One thing I really like about being here is the drive to translate from bench to bedside. I think that is such a huge focus, and here they are really trying to make that a reality.” Goldsmith continues to focus on neuroblastoma research at the Aflac Cancer Center, where her laboratory is working on determining how and why certain cells become resistant to chemotherapy, develop profiles of these cells and then develop alternative treatment options—bringing better drug therapies and hope to those with the most high-risk, difficult to treat types of tumors.

Neuroblastoma is the second most common solid tumor among children after brain tumors. While a low-risk tumor is highly curable, high-risk neuroblastoma tumors kill more than half the children suffering from the disease. “Children are most likely to die from recurrent disease because the cancer becomes resistant to chemotherapy,” said Dr. Goldsmith, who is also Assistant Professor of Pediatrics at Emory University’s School of Medicine.

“For this particular tumor, we have to figure out a better way to make the children chemotherapy- sensitive again, or to therapeutically target the tumor without harming normal tissues,” she continued.

Goldsmith and her team are working to identify the causes of chemotherapy resistance in neuroblastoma and test new treatment options. By screening tumors to determine optimal options of treatment and using combination therapies with these findings, ideally, goldsmith can help develop a less toxic and more tumor-specific therapeutic option for children with highly chemo-resistant solid tumors.

Goldsmith’s work is concentrated on the study of a family of proteins, BCL-2, which can either promote or prevent the programmed cell death (known as apoptosis) that is triggered by chemotherapy. Dr. Goldsmith’s research has found that BH3-only proteins can trigger apoptosis, and she and her team have determined that small chains of amino acids called BH3 peptides can mimic these proteins and kill neuroblastoma cells in test tube cells and mice. The goal of her work is to continue to isolate these cells in order to determine which drugs are best used in neuroblastoma treatment.

“But establishing the effectiveness against cancer cells in test tubes and live test subjects is just the first step in treating children with this disease,” said Dr. Goldsmith.

“The next phase of research requires fresh neuroblastoma tumor tissue, but demand is extremely high for the limited tissue available, so new techniques are needed to reduce the demand of tissue needed for experiments.” In order to address this need, Goldsmith worked with colleagues to adopt an improved method for screening and selecting human tumor samples used in their research. However, she needed expensive laboratory equipment in order to use this new method in her research.

Enter CURE, whose funding allowed goldsmith and her team to purchase a BIOTEK multiwell plate reader, which is crucial to carrying out this new method for identifying tissue samples as well as many additional planned studies and experiments.

“Because of CURE’s generosity and this new reader, I can focus on how effective these BH3 peptides are in killing neuroblastoma in actual human cells,” said Goldsmith.

“We can also combine these peptides with additional drugs already known to inhibit the proteins that help cancer cells grow and thrive. This will not only help us develop more tumor- specific, less toxic treatments for children with highly chemo-resistant neuroblastoma tumors, but ultimately, lead to a cure for this devastating disease.”