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Summer 2018 : Moon Shot team wants to know the whys of certain blood cancers
Moon Shot team wants to know the whys of certain blood cancers
Researcher and a clinician search for answers to tough questions about myelodysplastic syndromes and acute myeloid leukemia
Simona Colla, Ph.D., right, works with colleagues to understand why some patients with myelodysplastic syndromes respond to therapies and some don’t. Photo by Adolfo Chavez III
Why do current therapies used to treat myelodysplastic syndromes (MDS) fail in most patients? Why do some people have a greater risk of developing acute myeloid leukemia (AML) after being treated for other cancers?
There are no easy answers to questions such as these, which drive the work of Simona Colla, Ph.D., and Koichi Takahashi, M.D. But together, Colla — a researcher who uses mouse models of disease to unravel biological pathways — and Takahashi — a physician scientist who specializes in complex genetic analyses — are approaching complex questions from multiple angles.
The answers may mean the difference between life and death for patients, which is precisely what fuels the duo's work on one of the central projects of the MDS and AML Moon Shot™. That project focuses on understanding and overcoming the challenges associated with pre-leukemia and MDS.
Words of wisdom
Before becoming an assistant professor of Leukemia, Colla was an instructor in the laboratory of former MD Anderson President Ron DePinho, M.D. It was there that her interest in MDS research was sparked while working with a strain of mice that developed the disease.
A bit of advice from DePinho, a professor of Cancer Biology, helped refine that interest.
“One thing that Dr. DePinho always taught me was when you have the possibility of doing impactful research you need to understand which is the most important question,” Colla says.
From Guillermo Garcia-Manero, M.D., co-leader of the Moon Shot and professor of Leukemia, she learned the most important problem for MDS patients is the failure of standard therapies known as hypomethylating agents (HMAs).
“For MDS, the only cure is not a cure,” Colla explains. “The majority of patients either do not respond to therapy or relapse.”
To understand why HMAs ultimately fail, Colla began an ambitious project funded by the Moon Shots Program™.
An analysis of more than 250 samples from patients with MDS, taken at different stages of disease, revealed HMAs eliminated the mature cancer cells but left stem cells alive, leading to relapse.
The team discovered patients could be divided into two groups based on a profile of those stem cells. According to Colla, each group is biologically distinct, and requires different approaches to overcome resistance to HMAs.
Colla's group already has made progress in finding drugs that may be able to treat these two subgroups, and they continue their work to advance these therapies to the clinic.
Koichi Takahashi, M.D., studies genetic mutations that cause cancer. Photo by Adolfo Chavez III
The patient encounter
As a clinician, Takahashi is motivated by his interactions with patients.
“The encounter with my patients really drives me. I can see the unmet needs from my direct contact with them,” the assistant professor of Leukemia says. “In the clinic, patients often ask very good questions, and if I don’t have an answer, that drives my research.”
Takahashi came to MD Anderson as a clinical fellow, during which time he began working with Andy Futreal, Ph.D., co-leader of the Moon Shots Program and chair of Genomic Medicine. That work cultivated his interest in the genetic mutations that cause cancer, but he has always been drawn to leukemia because of the challenges it presents to patients.
“Having leukemia, patients are really facing serious life or death issues, and I wanted to help in those difficult times,” he says. “I know that research can really affect those outcomes, and I thought it was a good way to dedicate myself.”
For the moon shot, Takahashi's focus is on understanding the pre-leukemia state, before cancer has even developed. A better understanding would allow him to diagnose the disease early, and perhaps even prevent it in those at high risk.
In a rare subset of patients, the treatments themselves can lead to the development of MDS or AML. By studying DNA from these patients, Takahashi identified specific genetic mutations that predispose some people to a higher risk of therapy-related leukemia.
The Moon Shot team is working to learn why these mutations can cause the diseases.
Once that is known, they can identify and test drugs to prevent it.
A revolutionary approach
Colla and Takahashi both credit the Moon Shots Program for enabling them to pursue their research through seamless collaboration with world-class scientists and clinicians at MD Anderson.
“For us, the moon shot was revolutionary,” Colla says. “That was a reality you cannot have at other great universities. These are the best doctors in the world.”
Not only does the Moon Shots Program fund these investigations, it provides valuable technical expertise and infrastructure through its research platforms, Takahashi says.
“It's an unbelievably unique environment we are in here,” he says. “I think it will have a huge impact, not only on MDS and AML, but in other solid tumors as well. This is a very, very unique program.”
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