November 21, 2016 | by Hannah Glenn
Weili Sun, M.D., Ph.D., had a sister she never met. Her sister, Weiwei, was diagnosed with acute lymphoblastic leukemia (ALL) in the 1960s, before Sun was born. ALL is the most common form of leukemia in children, and at that time there was really no treatment for it.
Sun recalls her mother telling of the pain she endured watching her first daughter go through almost daily spinal taps to relieve pressure from leukemia cells building up in her spinal fluid and then watching Weiwei finally succumb to the disease. Sun carried this early memory into her Ph.D. studies, and it contributed to her focus into clinical research for developing new treatment options for children with leukemia. She feels that no family should ever go through what her parents or sister went through.
Today, the survival rate for ALL in children is around 90 percent, and the survival rate of acute myeloid leukemia (AML), around 60 percent. Sun attributes this drastic improvement to the number of clinical trials and advancements in research – one of her major interests in joining City of Hope as an associate clinical professor in the Department of Pediatrics and as the director of pediatric leukemia earlier this year. Double board-certified in pediatrics and pediatric hematology and oncology, Sun comes to City of Hope from Children’s Hospital Los Angeles and Keck School of Medicine of USC, where she was an assistant professor in the pediatrics department.
Here, we speak with the pediatric oncologist about her background and vision for the future of leukemia research and treatment.
What type of research do you do? What are some specific areas you like to focus on?
I'm doing mostly clinical research. I'm really focused on new drug development, so early phase clinical trials. I work very closely with the lab scientists. Because of my Ph.D. background, I understand what they're doing and if they have any promising new agent, I help them develop a clinical trial to bring it from the bench to the bedside and test in children with leukemia.
What are some exciting possibilities for new therapies that you have found in your research?
Before joining City of Hope, I ran a multicenter of phase 1 clinical trial combining epigenetic therapy with chemotherapy to treat children with relapsed leukemia. We were actually able to find a biomarker that's highly associated with response to treatment.
Now we are testing this biomarker in more patients to see if will be able to use it to direct what kind of therapy a particular patient can receive.
Can you explain epigenetics in relation to leukemia treatment?
Yes. Let me talk about genetics first. Genetics is the DNA. When you have a genetic change, that means your DNA actually changed and mutated, which can lead to developing cancer that is more resistant to therapy. Once this change happens to the DNA, you cannot reverse it.
Epigenetics is actually not a change in the DNA, but a change in how we can make a protein from the DNA. So it's above or on top of the genetics. The beauty of epigenetics is that we found out the epigenetic change is also very important for the development of cancer drug resistance and relapse. And because it doesn't change the sequence of DNA itself, the changes in the epigenetics can be reversed by medication.
For example, methylation is one of the major things in epigenetics that actually can be reversed by epigenetic modification. So the idea is if the disease relapses or if a patient is resistant to the treatment, it's because they have epigenetic changes, and we can give epigenetic modifiers to reverse those changes. Then we can give them chemotherapy since they have regained the sensitivity to it.
What are some common signs and symptoms for leukemia in children?
Common leukemia symptoms and signs are not very specific. A lot of patients have fever, bone pain or body ache, they bruise easily, have nosebleeds, their mouth might bleed when they brush their teeth, fatigue. Very nonspecific. But it's not hard to diagnose. It's just a simple blood test to identify it.
What are your goals and priorities for your work here at City of Hope? How much of a role does research play?
I think my goals and priorities are divided into two parts – the clinical part and the research part. But those are actually closely related. Let me start with the research part. My particular interest is in pediatric AML, which is a less common leukemia in children and more common in adults. There are lots of great clinical trials going on in adult wards, but we haven't started it in pediatric AML wards yet.
One of the major reasons I came to City of Hope was I wanted to work with the adult AML scientists and clinical investigators here to bring the promising new therapies that have been tested in adults to the pediatric patients with AML.
So my clinical goals would be to expand the pediatric leukemia program here. The strategy for expansion is to open more clinical trials that are only available here at City of Hope because we have the opportunity to work with our adult colleagues, which is quite unique to City of Hope, and bring that to the pediatric ward. So I work very closely not only with our adult colleagues, but also with other lab scientists as well. I try to understand what's going on in the lab and also provide some input from clinicians.
What does success look like for you in terms of your work trickling down into the day-to-day lives of a patient? Say 10 or 20 years from now what are you hoping to accomplish with your research?
The ideal goal is in the future when a patient is diagnosed, we will be able to quickly do genetic and epigenetic tests to figure out exactly what changes they have and then give them very personalized therapy that will best treat their cancer and at the same time eliminate unneeded toxicities – so, a more personalized approach.
What advice do you have for children and families of those recently diagnosed with leukemia?
I think it's terrible that your child is diagnosed with cancer. It's devastating, but keep in mind that children are very strong. They're very resilient and with current therapy most children can grow up and go to college and everything. So you just need to keep it together and support each other, and also work with the doctors and nurses as a team, and then most kids will do fine.
Anything else you think is important that you want people to know?
I hope people will support pediatric hematology and oncology research. In terms of the drug development, pediatric oncology is often overlooked because, fortunately, not many kids get cancer. Due to the small patient population, a pharmaceutical company may not be very interested in developing drugs explicitly for pediatric oncology because of the lack of financial incentive.
It's very expensive to develop a drug and sometimes it's hard for us to do clinical trials. So a lot of times, we rely on the private foundations and donors. I want people to know there are a lot of kids being treated, but we can't cure everybody yet and we need help and more support.