Facilitate the transition of projects from the laboratory to the clinic. Translational researchers seek to apply basic knowledge of cancer and bring the benefits of the new basic-level understandings to patients more quickly and efficiently. These grants are $600,000, three-year commitments
Funded by the Dick Vitale Pediatric Cancer Research Fund
Immune checkpoint inhibitor therapy (ICT) is a form of cancer therapy that boosts the immune system to kill cancer cells. ICT can help cure some adult cancers but has not been effective in children with cancer. This proposal explores whether a combination of standard cancer therapy and ICT is both safe and effective in children with solid tumors in a clinical trial. First, we will test tumor, blood, and stool samples collected from patients in this clinical trial. We will attempt to learn what factors determine whether a patient will respond to this combination therapy or not respond. Second, we will use mouse cancer models to test different combinations of standard cancer therapy and ICT to see which combinations work the best. This work will help us understand if combining standard cancer treatments with ICT is both safe and effective in children with solid tumors.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Osteosarcoma (OS) is a cancer of the bones that affects up to 500 children, teens, and young adults each year. While current therapies are effective for many patients, patients that have multiple tumors or have tumors that do not respond to chemotherapy have poor outcomes. CAR T cells are a therapy that uses the immune system to fight cancer. CAR T cells have been successful in patients with blood cancers that no longer respond to chemotherapy but CAR T cells have had limited success in solid tumors. My lab has developed a new form of CAR T cells that are more potent and last longer in the body. This project will explore whether our new CAR T cells can work against OS. OS is a common cancer in dogs and OS in dogs is very similar to OS in children. The Flint Animal Cancer Center is internationally recognized for running cutting edge clinical trials for dogs with cancer. This project will test our new CAR T cells in pet dogs that have OS and are in need of advanced therapies. Since OS is very similar between dogs and children, making a therapy that is effective in dogs will produce valuable data for developing a clinical trial for children with untreatable OS.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Hockey Fights Cancer and Jeffrey Vinik
The most common cancer in children, including teenagers, is a blood cancer named leukemia. Chemotherapy is the main treatment for pediatric leukemias. Although most patients respond well, some do not, leading to poor outcomes. Chemotherapy can also have negative side effects both during treatment and for the rest of their lives.
Patients who don’t get better with chemotherapy are those that have one of most common genetic changes, the rearrangement of a gene called KMT2A (KMT2A-r). In a study at The University of Texas MD Anderson Cancer Center, patients with KMT2A-r leukemia survived for 6 months after 2 chemotherapy treatments and only 2.4 months after 3 or more treatments. Scientists are looking at new ways to treat these patients and help them live longer.
Menin inhibitors could be a good option because they target KMT2A-r leukemia and have fewer side effects than chemotherapy. But some patients with KMT2A-r leukemia can also have mutations in other proteins that don’t let the menin inhibitors work as well by themselves.
With the help of the V Foundation, Drs. Andreeff, Carter and, Cuglievan, at MD Anderson Cancer Center plan to test different combination treatments that target menin and other proteins at the same time to get better results. This can potentially help children with KMT2A-r leukemia live longer and have better lives.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Malignant rhabdoid tumors and epithelioid sarcomas are rare cancers that can develop throughout the body. Sadly, these tumors are often deadly for patients who can’t have surgery or whose tumors don’t respond to chemotherapy. Recently, a new drug called tazemetostat has been approved to treat these cancers, but only about 15% of patients get better with it. Our new research project explores DNA damage repair and targeting its mediators in tumors cells to offer new treatments to patients. Our past research shows that a protein called ATR is important for the growth of tumor cells. It is possible that other similar proteins are necessary for tumor growth and is therefore important that we study them to understand if ES and MRT patients may benefit from other drugs that interfere with these processes. For example, we found that combinations of drugs, chosen logically based on research evidence, is more effective in controlling tumor cell expansion, when compared to using drugs alone. We plan to find the best combination of novel drug inhibitors to stop these tumors from growing. We also want to understand how these drugs work in the body so we can predict which patients will benefit the most. This research should lead to a new, safe, and effective treatment for many patients with RT and ES who currently have no cure. The findings might also help treat other types of childhood and young adult cancers, creating a roadmap for difficult to treat tumors.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Hockey Fights Cancer and Jeffrey Vinik
Diffuse midline glioma (DMG) is a very aggressive brain tumor that occurs mostly in children. DMG treatment involves surgery, radiation, and chemotherapy, but most people with DMG don’t live longer than a year despite these treatments. We desperately need better therapies for this disease. Treating DMG is difficult because tumors aren’t the same in every person, so a drug that works for one person might not work for another. Therefore, we need treatments that are personalized for each patient. In addition, different parts of the tumor may not all respond to the same drugs, and we might need to use a mixture of drugs to eliminate the whole tumor. And even if we find drugs that do this in the lab, getting them into the tumor is tricky because of the “blood-brain barrier”, which prevents many drugs from getting from the bloodstream into the brain. We are proposing a new approach to DMG treatment that overcomes these challenges. To find individualized treatments, we will test many different drugs on tissue from surgery or biopsy to see which ones work best for each patient. We’ll also look at the effects of drugs on individual cells in the tumor and find the combinations of drugs that kill the most tumor cells. Finally, we’ll use a method called convection enhanced delivery (CED) to pump drugs directly into the tumor, bypassing the blood-brain barrier. By using these approaches, we will find better treatments for DMG and other brain tumors in kids.
There is a need for new treatments that increase survival for advanced prostate cancer (PC) patients. Doctors mostly still rely upon hormone therapies for PC, but patients become resistant to these drugs. Sometimes this resistance occurs through developing neuroendocrine (NE) PC. This change is controlled by enzymes that regulate the gene expression programs. Many patients have mixed tumors with both forms of PC. Unfortunately, such patients have poor clinical outcomes. Therefore, it is important to identify drugs that can treat both to increase patient survival. One approach is to target lysine-specific demethylase 1 (LSD1), one of the key enzymes needed for NEPC transformation. In this study, we will be using tumor tissue from PC patients treated with a drug targeting LSD1. This will help to identify patients that will benefit from this treatment and better direct patient selection in future clinical trials.
Colon cancer is a devastating disease. It is one of the leading causes of death from cancer, even after decades of research. Scientists have found that cancer changes the way cells use nutrients to grow rapidly and spread to other parts of the body. Inside cancers cells, specialized factors called enzymes help cancer do this. These enzymes help cancer cells use particular nutrients to keep growing and living. There is one kind of enzyme, called creatine kinases (CKs), that are extremely important for colon cancer cells but not for healthy ones. Because of this, we think we might be able to create a medicine that attacks CKs to treat colon cancer without affecting the rest of the body.
We have developed a new medicine that stops CKs and is effective at killing cancer cells that need CKs to live. Our plan is to develop this medicine to work in animals with colon cancer. This is the critical first step before we can try it in people. If we succeed, we could have a brand-new way to fight colon cancer by stopping the CK enzymes that cancer needs to grow and spread. We hope that this new treatment could be very strong against colon cancer that has spread to other parts of the body.
KRAS mutations are common driver mutations in cancer (ie a mutation that makes the cancer come to be) and particularly common in GI cancers. There are new drugs that target these KRAS mutations. Some drugs cover all KRAS and RAS mutations and some cover specific mutations but the drugs work for short periods of time, even when they work, and many patients still do not benefit at all from these drugs. We are trying to understand why the drugs do or do not work and ways to not only make the drugs work for more people, but when they work, make them work for longer periods of time.
Colorectal cancer (CRC) remains a major cause of cancer-related deaths, mostly due to the risk of cancer metastasis to the liver. This is because while we can detect and treat cancer that is limited to the primary location, we are, till date, unable to treat cancer that spreads to other parts of the body, creating the urgent need for new, life-saving treatments to fight cancer spread. Several studies have established that long-term use of aspirin, a common and inexpensive medicine, can help lower the risk of CRC. However, recent results from studying patients surprisingly showed that aspirin can increase the risk of cancer metastasis and death, especially among older adults. We further discovered that while aspirin may slow down how CRC starts, it can also help the growth of tumors after they have spread to the liver. We also found that this unexpected effect of aspirin on cancer spread is via suppressing the body’s immune system and its ability to fight cancer cells. This means drugs that counter the effect of aspirin may be able to help our immune system fight cancer spreading to the liver. We propose to understand how aspirin influences the immunity in the liver to fight cancer, as well as test whether drugs that oppose aspirin’s effects can inhibit cancer metastasis. We will also test the association of aspirin with metastasis within CRC patients. Ultimately, our new understanding of this process will help us build new treatments to fight cancer that spreads to the liver.
MDS and AML are two types of serious blood cancers called leukemias, with low chances of survival. Doctors usually look at genetic changes to decide how to treat them, but other things can also affect how well the treatment works. Older MDS and AML patients often get a medicine called a hypomethylating agent (HMA), sometimes with another drug called venetoclax. But only a small number of people respond well to HMAs. So some people end up getting treatments they don’t really need, and also might have side effects. Unfortunately, there is no test that can tell which patients will improve with HMAs and which ones won’t. We have two main goals: (1) to make a test to predict who will respond well to HMAs, and (2) to find ways to make the cancer cells more likely to respond to the medicine. We hope that this test will help doctors to choose the best patients to receive HMAs. In the long‐term we hope to find a better way to treat those patients who don’t respond to HMAs. We hope this research will help patients by not having them take medicines that won’t work, so they don’t get unnecessary side effects. In this way, they can also immediately get a different medicine that might work. Ultimately, we hope the new medicines we discover will help improve survival for more patients with leukemia.
