Childhood Cancer

Ewing's Sarcoma

Ewing’s sarcoma is a cancerous bone tumor that typically originates in the long bones of the arms and legs, the pelvis or the chest. While it is typically a bone tumor, Ewing’s sarcoma can develop in the soft tissue surrounding the bones as well. It is often diagnosed during puberty, when the bones of the body are rapidly growing. 

Latest Ewing's Sarcoma grants

Patrick Grohar, MD/PhD, Principal Investigator
Van Andel Research Institute
Innovation Grants, Awarded 2017
Alejandro Sweet-Cordero, MD & Maximillian Diehn, MD/PhD (Stanford University), Principal Investigator
The Regents of the University of California San Francisco
Innovation Grants, Awarded 2016
Elizabeth Lawlor, MD/PhD & Deneen Wellik, PhD, Principal Investigator
University of Michigan
Innovation Grants, Awarded 2016

Latest Ewing's Sarcoma blog posts

July 14, 2017

by Trish Adkins

It all starts with what seems to be normal pain and a bump. 

To a parent, their child is just complaining about something painful on their arm, leg or pelvis. The pain worsens. The bump lingers. And after many visits to the doctor, a diagnosis is finally made—Ewing’s sarcoma, the second most common type of childhood bone cancer

What appears on an MRI as a large tumor in the bone and growing into the adjoining tissue of the body, is really the result of one of the tiniest parts of the human genome—a single abnormal oncogene, known as EWS-FLI1. It is this oncogene that orchestrates a single cell’s conversion into an Ewing’s sarcoma tumor.

Turning off this oncogene may lead to a cure for Ewing’s sarcoma. The only trouble is that scientists continue to struggle with how to turn it off.

Trading Places: Chromosomal Translocation
Prior to the discovery of EWS-FLI1 in 1992, misdiagnosis was common because the cells of Ewing’s sarcoma and other cancers looked similar under the microscope. Now, doctors know that a tumor is Ewing’s sarcoma if EWS-FLI1 is present in the patient’s cells.

EWS-FLI1 is the result of a complicated and fascinating process called chromosomal translocation, which happens when a portion of one gene trades places with a portion of another gene and causes an abnormal chromosome fusion within a single cell in the body. Once created, EWS-FLI1 begins a very precise process of turning other genes on and off in a specific pattern to drive the growth of Ewing’s sarcoma. Tumors typically occur in the bones, but they can also arise in the connective tissue or even sometimes within the organs in the body. 

For the majority of children diagnosed with Ewing’s sarcoma, the disease is localized and has a 70% chance of being cured. For the other children with metastatic disease that has spread from the original site, a cure can be elusive and only 20% of these children will survive their cancer.

Removing EWS-FLI1 from the cells of the body seems to be the logical cure. In the lab, researchers are able to remove it, causing the tumor cells to die. So, why can’t doctors simply turn off this oncogene in children battling Ewing’s sarcoma?

That, says Dr. Stephen Lessnick, a member of the ALSF Scientific Advisory Board and physician-scientist at Nationwide Children’s Hospital in Columbus, OH, is the million dollar question.

“We need to unlock the puzzle by using research to find the critical pieces of information that show how this oncogene causes Ewing’s sarcoma,” said Dr. Lessnick. “Once we know more about how EWS-FLI1 works, then we will be able to figure out exactly how to block its function.”

Finding Drugs That Stick
There are several important discoveries, powered by ALSF-funded researchers, that are moving them closer to unlocking this puzzle. Dr. Lessnick points to two approaches that are working to end the reign of EWS-FLI1. 

One approach is to target the oncogene itself (or more properly, the protein that is made by that oncogene). For years, this has been challenging. For a medication to work, it has to stick to something useful inside the cells, according to Dr. Lessnick.  “Molecularly-targeted” childhood cancer drugs that work find a tiny pocket in the protein, settle into that spot and prevent that protein from working properly thereby ending its ability to cause cancer cell growth. 

Unfortunately, EWS-FLI1 is not thought to contain any pockets for a drug to be effective. However, Dr. Jeffrey Toretsky, a researcher at Georgetown University and recipient of an ALSF Innovation Grant is currently in a Phase 1 trial of a drug that appears to block some of the function of EWS-FLI1 by sticking to it via a yet-to-be-discovered mechanism.

Another approach, which Dr. Lessnick is studying, is to target the other enzymes that EWS-FLI1 itself sticks to and uses to drive the growth of Ewing’s sarcoma. One of these enzymes, LSD1, works in concert with several different oncogenes, including EWS-FLI1. Using a drug that was created to target LSD1 in breast and prostate cancers, Dr. Lessnick and colleagues have demonstrated that the drug kills Ewing’s sarcoma cells in the laboratory setting.  He believes this could be an important breakthrough in the treatment of metastatic and relapsed Ewing’s sarcoma. Working in collaboration with other scientists, Dr. Lessnick is close to bringing this therapy to clinical trial.

“Continued research and collaboration are so critical to advance our search for cures,” said Dr. Lessnick. “No one lab has the full complement of expertise to deliver a cure singlehandedly. It’s only by working together that we will find answers and cures.”

Read more about Ewing's sarcoma and ALSF funded projects here

July 2, 2017

 

by Maya Rigler, Childhood Cancer Hero

Alex’s Lemonade Stand Foundation has been a part of my life for as long as I can remember.  Although I never met Alex, her story has always impacted me. We both fought cancer and were even treated at the same hospital with some of the same doctors. Her home is just a few miles away, and she’s been a hero of mine for as long as I can remember.

Just before my second birthday, my doctor discovered a mass in my stomach. I found out I had a type of cancer called Wilms' tumor in my kidney. I had to undergo chemotherapy and radiation for eight months. I don’t remember that much of it, mostly sitting in hospital rooms and watching Elmo while getting chemo. I had to miss a lot of preschool for treatment! I had to get surgery to remove one of my kidneys since it had a tumor on it, so I’ve always had to drink a lot more water than my friends. During treatment, my family was introduced to ALSF. 

My two younger brothers and I hosted lemonade stands every year. Each year, we brought the money from the lemonade stand to Alex’s “Original” Lemonade Stand at Penn Wynne Elementary School. It became an annual family tradition. I would have never imagined that the disease I barely remembered would soon become a much greater part of my life.

When I was ten years old, my parents took me to the doctor’s office because something seemed off. I was taken to Children’s Hospital of Philadelphia (CHOP) to be checked out. The doctors told me it looked like I had a mass in my stomach and that we just needed to find out what was going on. I heard the doctors use the term “mass,” I immediately gave it a name - Bob the Blob! After a week, we found out that Bob the Blob was a type of cancer called Ewing’s sarcoma in my pancreas. Within days of being diagnosed, I had countless gifts arrive at my hospital door. So many people were extremely generous, but I thought about the other patients on the oncology floor, who might not feel the same support that my family was feeling. My cancer had a cure, but some of theirs didn’t.

I decided to start up a virtual fundraising page on Alex’s Lemonade Stand Foundation’s website. In just a few weeks, we were up to $100,000! The immense happiness I got from knowing I could make a difference, even at such a young age, was way better than any presents.

I began chemotherapy and six weeks of radiation. I was in and out of the hospital for many days at a time, and I had different surgeries. I saw many doctors, too. One time, a doctor had on an Alex’s Lemonade lanyard. I jumped and asked her how she was involved. The doctor told me that she was a researcher and that ALSF helps fund her research to help find a cure for childhood cancer! The doctor tested my tumor and was able to tell me that my two cancers were unrelated. It is amazing to know that ALSF helped make a difference in my own treatment! 

Even with support, love and a strong community surrounding my family, having cancer at any age is really hard. I learned so much about helping others while I was sick. It was incredible to see the donations pouring in from everyone who donated, no matter how much, to help find a cure for this horrible disease. I was so thankful, and soon we had reached $250,000. I was in awe of how much of a difference one person could really make. Through things like Instagram, Facebook and the ALSF website, I was able to share my story. Once the idea caught on, the local news covered my story and the stand took off even more! It was amazing to see what could happen when you ask for help. My friends and family began hosting lemonade stands on their own to help benefit my page. As of today, I have raised a total of $410,010!! 

If you’re reading this and think one person can’t make a big difference, think about what Alex Scott said “when life hands you lemons, make lemonade.”

Maya Rigler is 13-years-old and a two-time cancer survivor. In 2016, she was honored at the Lemon Ball as Stand Host of the Year.