2025 Archives - Page 4 of 8

Toshiro Hara, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Brain cancer is an unwelcome guest that sneaks into a kid’s brain. Doctors can usually see and take out the cancer, but it gets really difficult when the cancer enters normal brain areas. This sneaky move by cancer is called invasion. The problem is that these cancer cells are so small and tricky that even our best medical scanners can’t find them. It is like the cancer is playing a game of hide-and-seek in the kid’s brain and escaping from the doctor’s tools.We know some of the places the cancer hides, but we don’t understand why it chooses certain paths or how it moves so easily. So, what we did was take a super close-up look at how brain cancer behaves using a special research tool. This is a way to see exactly what is going on inside individual cancer cells. Our first look tells us that brain cancers are like masters of disguise — they can look like normal brain cells, especially when they are hiding among them, and it seems they might even be “talking” to the normal cells around them.We will dive deep into how these cancer cells chat with healthy brain cells and what special tools or genes they use to travel so well. We believe figuring this out could put the brakes on cancer’s sneaky move. It could lead to new treatments that stop their play and talk, making treatment much more effective and helping many kids.

Jeffrey Magee, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

My lab is working on new treatments for children with hard-to-cure cancers. We focus on a type of cancer called acute myeloid leukemia, or “AML” for short. AML accounts for about one-third of childhood leukemias. We have been less successful at treating AML than other childhood cancers. AML is challenging to treat because each patient may have different genetic mutations (alterations) causing their disease. A new drug that works for one patient might not work for another. Also, drugs that work in adult AML patients might not work well for childhood AML. To get around these problems, we create models that accurately reflect human childhood AML. We have created many different models to include the different types of mutations that patients can have. While studying these models, we discovered a protein called SPNS2 that might be a new drug target for tough AML cases. Early tests with an SPNS2 drug show promise in killing AML cells. This project aims to find out which patients will benefit most from SPNS2 drugs and see if combining these drugs with other AML drugs could improve treatment even further. We also aim to understand why SPNS2 is important in these cancers. My goals are to improve treatments and to broaden our understanding of AML in children.

Ulrich Steidl, MD, PhD

Acute Myeloid Leukemia (AML) is a fast-growing blood cancer that is very hard to treat. Fewer than 20% of patients live more than five years after being diagnosed. One big problem is that AML often comes back after treatment or stops responding to chemotherapy, which is the main reason people die from this disease. Most research has looked at genetic changes that help cancer cells resist treatment, but new studies show that non-genetic changes also play an important role.Our research focuses on one of these non-genetic factors called “transcriptional noise.” This means natural changes in how genes are turned on and off in cells. Using advanced tools that look at single molecules, we found that chemotherapy causes a quick increase in this transcriptional noise. This seems to help leukemia cells survive the treatment. When we blocked this noise—by targeting an enzyme called Pol II that controls gene activity—the leukemia cells became more sensitive to chemotherapy. We saw this in lab tests and in mouse experiments. We also found that certain “early response” genes—genes that react fast to chemotherapy—show a lot of this noise, which means they could be new targets for drugs. Our future research will try to figure out exactly which genes are involved, how this noise helps cancer resist treatment, and which types of AML can be treated better by blocking transcriptional noise. This new approach could lead to better ways to stop drug resistance in AML and other cancers, giving patients hope for more successful treatments in the future.

Christina Curtis, PhD

Why do some people get certain types of cancer, while others don’t? For some cancers, we know that inherited genes play a role. But for many, it’s still a mystery. One reason is that cancer is very complex and we don’t fully understand how a person’s genetic makeup and immune system affects their risk.In our recent research, we found something surprising. We discovered that both a person’s genes and their immune system work together to influence which type of cancer they might develop. This includes hard-to-treat types like HER2+ and ER+ breast cancer, which can come back many years after treatment.Some early changes in a tumor’s DNA can act like a warning signal, helping the immune system find and destroy these abnormal cells before they grow. But if the tumor hides from the immune system, it can become more dangerous. That’s why it’s so important to find and treat these cancers early.Our work helps to explain the role of genetic variation in cancer, even when no single gene seems to be responsible. It also points to new ways to determine who is at risk and to create treatments that are personalized—based on each person’s genes and immune system. We’re working to turn these discoveries into better tools to predict, prevent, and treat cancer more effectively.

Britta Will, PhD

Acute myeloid leukemia (AML) is a deadly blood cancer that starts in the bone marrow, where our blood cells are made. This cancer is especially dangerous for people over 65 – more than 9 out of 10 patients die from it. The treatments we have now work for a while, but then they stop working. This happens because some cancer cells are tough and can survive the treatment, causing the cancer to come back. Scientists have discovered something important about how these cancer cells survive. They found that the way cancer cells use iron helps them fight off treatment. Iron is a mineral our bodies need, but cancer cells change how they handle iron to stay alive when doctors try to kill them. We believe that iron helps cancer cells resist drugs that are supposed to make them grow into normal, healthy blood cells. We made an exciting discovery: when they used drugs that grab onto iron, the cancer cells became much easier to kill with regular treatments. This seems to work on many different types of this blood cancer, even the hardest ones to treat. We plan to test this new approach by mixing iron-grabbing drugs with current treatments. We will use real cancer cells from patients to see if this combination works better. We want to find out if it can really get rid of the cancer stem cells (the “parent” cells that keep making more cancer). If this research works, doctors could have a new way to treat older patients with this blood cancer. Many older patients can’t get bone marrow transplants because they’re too risky. By targeting how cancer cells use iron, doctors might be able to beat treatment resistance and help patients live longer without using harsh chemotherapy drugs.

Chonghui Cheng, MD, PhD

Cancer vaccines are a promising new treatment that help the immune system find and destroy cancer cells. These vaccine work by teaching the body to recognize special signals, called neoantigens, that appear only on cancer cells. Most cancer vaccines today use neoantigens caused by changes in DNA. But because these changes are different for each person, it is hard to make a vaccine that works for everyone. Our research aims to develop a more widely useful cancer vaccine for triple-negative breast cancer (TNBC), a fast-growing and hard-to-treat cancer. We are studying a new type of neoantigens, that comes from a mistake in how cells process RNA. Normally, cells remove parts of RNA called introns before making proteins. But in some cancer cells, this process fails when a protein called hnRNPM is missing. As a result, the introns stay in, leading to unusual protein pieces that the immune system can recognize and attack. Our team includes experts in RNA, data science, and vaccine development. We are working together to find common neoantigens in TNBC that come from faulty introns and to make a strong mRNA cancer vaccine. We will look for the most common neoantigens made this way in TNBC and build better tools to find neoantigens that current methods miss. We will create mRNA vaccines that teach the immune system to attack these cancer signals. If this works, the vaccine could help treat TNBC and possibly other cancers that make the same neoantigens.

Djordje Atanackovic, MD

Bob Bast Translational Research Grant*

T cell acute lymphoblastic leukemia (T-ALL) is a serious cancer that affects part of the immune system called T cells. It’s especially hard to treat in adults, and current treatments often don’t work well. A special treatment called CAR T cell therapy—where doctors change a patient’s own immune cells to fight cancer—has worked well for some other types of cancer. But using it for T-ALL has been very difficult. One problem is that the CAR T cells can accidentally attack healthy T cells, and sometimes even attack each other.We recently identified a new target called CD229, a marker found on both cancerous and some healthy T cells. We made CAR T cells that attack cells with CD229. The exciting part is that these new CAR T cells can still kill cancer cells but don’t harm as many healthy T cells. This is because healthy T cells lower the amount of CD229 when they are activated, so they are not attacked.We improved our CAR T cells even more by making them less “sticky,” so they are more careful about which cells they attack. Tests in the lab and in animals showed that these new CAR T cells still fight cancer well and are safer. Now, our team is testing this treatment on real samples from many T-ALL patients. If it works, we will start a small clinical trial. This new treatment could be a big step forward, giving hope to people with T cell cancers by offering a better and safer option.

Jessica Thaxton, PhD, MsCR

T cells are part of the body’s immune system. T cells ward off disease but are also capable of fighting cancers. In fact, immune therapies in cancers have produced major gains in allowing patients with cancer to survive long-term. T cells can invade cancers, but cancers create a hostile environment that limits T cell killing capacity. This makes immune therapies function poorly. We have discovered a pathway in T cells that is engaged by the hostile environment of tumors that induces T cell distress and death. We have found a group of drugs that inhibit this pathway. These drugs also protect T cells from sensing the stressful environment of cancer. This group of drugs allows T cells to live longer and fight harder to eliminate cancer. We have found that these drugs improve the long-term outcomes of immune therapies and hold potential to increase the number of patients cured of cancer when treated with immune therapy. This project plans to study this stress pathway in T cells in samples from patients with cancer and to test these drugs in several models so that they can be used in the clinic to fight cancer in patients.

Andrew Brenner, MD PhD

Some cancers can spread to the fluid that surrounds the brain and spine. This is called leptomeningeal metastases, or LM. It is a serious and often deadly problem. Today, there are very few treatments that work well for this condition.Our team is studying a new treatment called Rhenium Obisbemeda (186RNL). This treatment sends tiny amounts of radiation straight into the spinal fluid, where it can kill cancer cells. Unlike standard radiation, which can hurt healthy parts of the brain, this method targets cancer cells more carefully and reduces damage to normal tissue.In our research, we are collecting samples from patients to see how their cancer and immune cells respond to this treatment over time. We are also using lab models to test whether this radiation works better when combined with other treatments—like drugs that help the body’s immune system fight cancer or block cancer cells from fixing themselves.Our goal is to find safer and more effective ways to treat LM and possibly other hard-to-treat cancers. This research could lead to better options for people with advanced cancer, giving them more time and better quality of life.

William Freed-Pastor, MD, PhD

Pancreatic cancer is a terrible disease, and we urgently need better treatments. The immune system can search the entire body to find and destroy cancer cells, just like it protects us from viruses or bacteria. The immune system does this by recognizing small “flags” on the surface of cancer cells. Unfortunately, cancer cells can often “hide” from the immune system so they don’t get destroyed. We urgently need to find new ways to use the immune system to fight pancreatic cancer to develop better treatments for patients. We’ve been using something called “organoids” to study pancreatic cancer. These are tiny, 3D versions of tumors grown in a dish from a patient’s own cancer cells. Using these organoids, we’ve been able to identify the “flags” on the surface of pancreatic cancer cells that the immune system might be able to recognize. We’ve also created a special system to help us figure out which of these “flags” are the best ones for the immune system to fight and ultimately destroy the tumor. Our plan is to use what we’ve learned to carefully test many new targets on the surface of pancreatic cancers to see if the immune system can recognize them. This will help us develop improved therapies for pancreatic cancer patients.