Robert Hromas, M.D., a blood cancer expert at the University of Florida's College of Medicine, is looking to discover new drugs that will improve the response of elderly AML patients to chemotherapy. His latest research, funded through a Translational Research Program grant from The Leukemia & Lymphoma Society, focuses on inhibiting the DNA repair response.
How would you explain what kind of research you do?
The marrow inside your bones makes white blood cells, which fight infections. Most of these cells must be made new every day, because they only live for less than 24 hours. Once they are made, the bone marrow stops making more. Now imagine if the bone marrow never turned off making these white blood cells, and worse, they lived forever. Then your body would fill up with white blood cells, and this could kill you. This situation is called acute myeloid leukemia (AML). I study ways to kill these immortal leukemia cells in order to prevent them from killing you. Even more importantly, I have come up with some ways to prevent the marrow from making leukemia cells in the first place.
What is novel and innovative about your approach?
There are two novel aspects to our work. First, the most innovative part of what we do is study how to prevent the DNA mutations (called translocations) that cause leukemia.We have found that an FDA-approved ovarian cancer drug called olaparib can prevent translocations when given after a translocation-inducing toxin such as high dose radiation or high dose chemotherapy. The second novel aspect of our work is that we have described a DNA repair protein called Metnase that mediates resistance of leukemia cells to treatment. We have generated a new class of drugs that block Metnase from doing this. These drugs restore the sensitivity of leukemia cells to chemotherapy. Interestingly, these drugs are bi-functional, simultaneously damaging the leukemia cells’ DNA, and then inhibiting Metnase from repairing that DNA.
The Leukemia & Lymphoma Society (LLS) continually advocates for laws and policies to ensure that patients have access to lifesaving treatments. Our latest win came this summer when the U.S. House of Representatives approved the 21st Century Cures Act.
This bill, which is proof of LLS’s impact and would make a big difference for blood cancer patients, is now on Congress’ “to do” list.
The House of Representatives finished its work on the 21st Century Cures Act in July, leveraging the support of blood cancer patients and others to approve the bill with a huge, bipartisan majority. With Congress back in session, the Senate HELP Committee will now take up their version of the bill—an initiative they’ve termed “Innovation for Healthier Americans”—aimed at improving and accelerating the process to discover, develop, review, and approve new treatments for patients.
Matthew Matasar is a hematology and oncology specialist at Memorial Sloan-Kettering Cancer Center in New York City. He has a Translational Research Program grant through The Leukemia & Lymphoma Society and is investigating which Hodgkin lymphoma survivors are at greater risk for developing heart disease after receiving radiation therapy to the chest and what diagnostic tests are best.
What kind of research do you do?
There’s been a lot of progress in the treatment of Hodgkin lymphoma, but the treatments we use to cure the disease can lead to health problems later in life. Think of giving treatment for the disease as tossing a rock into a pond from the shore. The rock sinks to the bottom quickly, but it can take a long time for the ripples to reach you at the shoreline. Late effects from treatment are like that – it can take years, or even decades, before they become apparent. But we know that patients who get certain treatments are at increased risk, statistically, for a range of potentially serious medical illnesses. My research focuses specifically on trying to better understand who is at greater risk for getting heart disease after radiation therapy to the chest and, more importantly, what are the best tests available at finding heart disease before actual damage to the heart has occurred.
What is novel and innovative about your approach?
Our study will bring in as many as 200 long-term survivors of Hodgkin lymphoma who received radiation therapy to the chest at our center, Memorial Sloan Kettering Cancer Center. This will be the largest study of adult survivors of Hodgkin lymphoma ever performed. What’s more, we’re limiting this work to patients who don’t already have a diagnosis of heart disease. We’re looking only at healthy patients, because we’re interested in learning how to identify heart disease before heart damage occurs (seeing heart problems after the damage is done is, as you might imagine, much easier). All survivors will undergo two types of testing. First, a cardiac magnetic resonance imaging (cardiac MRI) both resting and after giving medicine to “stress” the heart, and second, an ultrasound of the heart (echocardiogram) both resting and after running on a treadmill.