Funded by the V Foundation’s 30th Anniversary Gala Event
Pancreatic cancer is the 4th most common cause of cancer death in the United States with one of the worst survival rates of any cancer. Patients with pancreatic cancer struggle to find clinical trials given the lack of options, the lack of any promising findings, the lack of functionality to tolerate many trials. Our research directly impacts cancer patients providing an innovative and promising therapy that has had success in other cancers. Our clinical trial will study pancreatic cancer patients receiving treatment with their own immune cells that we will have taken from their blood, re-engineered the cells to fight their cancer, and injected their re-engineered immune cells back into their body.Our research will study the blood from these patients and look for markers that are associated with treatment response in similar clinical trials. We will also study their tumor tissue before and after treatment and look to see if the injected, re-engineered immune cells were able to travel to the tumor, grow and thrives and kill cancer cells.
Funded by the V Foundation’s 30th Anniversary Gala Event
There is a new kind of cancer treatment called immune checkpoint blockade (ICB) that helps the body fight cancer by making the immune system stronger. Doctors use ICB with chemotherapy to treat triple-negative breast cancer (TNBC), but it doesn’t always work for everyone, so we need to find better ways to help these patients.
Scientists are studying tiny living things called microorganisms, like bacteria, that live in and on our bodies. These microorganisms can help us stay healthy and fight diseases. New research suggests that the gut microbiome—the collection of microorganisms in the digestive tract—might influence how well these treatments work. Some types of bacteria can help people respond better to the ICB treatment because they release beneficial metabolites.
In this project, scientists want to see if probiotics (which are good bacteria) or the beneficial metabolites they make can make the cancer treatment work better. They will look at samples from patients before and after treatment to see if these good bacteria and metabolites are helping.
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.
Funded by the V Foundation’s 30th Anniversary Gala Event
Despite its exciting impact, most cancer patients still do not benefit from immunotherapy. We have discovered a strategy used by cancers to avoid detection by the immune system. This work aims to use markers to determine which patients would be more likely to benefit from blocking this pathway in order to improve the effectiveness of immunotherapy. Using such a tailored approach is expected to enhance responses in a greater number of patients while avoiding the use and costs of ineffective therapies.
Funded by the V Foundation’s 30th Anniversary Gala Event
About half of all cancer patients will get radiation therapy (RT) as part of their treatment. But some cancers are naturally resistant to RT, and others become resistant over time. One idea to fight this resistance is to combine RT with treatments that boost the body’s immune response. In this project, we will test if a particular type of immunotherapy can overcome resistance to radiation and make RT work better. To check this idea, we’ll start by using lab mice to figure out the best way to do this treatment. These mouse tests will show us when to give the immunotherapy with RT for the best results. Once we know this, we’ll start a clinical trial with pet dogs that have cancer. The goals of this trial are to (1) prove that combining localized immunotherapy with standard RT is safe, and (2) show that this mix works better than just RT alone. The specific immunotherapy we’re looking at is called XCSgel-IL12. It’s a new type of treatment we made. It gets injected straight into the tumor, and it can be made in large amounts for a low cost. It looks very promising for beating radioresistance in many cancer types. This study will focus on soft tissue sarcoma. If it works well, we can start trials in humans with this type of cancer. It could also spark more research on combining RT with XCSgel-IL12 in other cancers in the future.
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.
A new kind of treatment for cancer that helps people’s bodies fight off the disease has allowed some patients to live longer, healthier lives. These new treatments, however, do not work for every type of cancer or for every patient. Solid cancers, in particular, are very good at protecting themselves from these therapies. Also, these new drugs are very difficult and expensive to make and sometimes can cause dangerous side effects.
The overall goal of this proposal is to make a safer and cheaper, but just as powerful, new treatment for solid cancers. For more than ten years, I have worked to develop better, safer cancer therapies. One of these new drugs was just tested in cancer patients and some people responded really well. When patients get this therapy, it acts like a delivery truck, dropping off special instructions to the body and teaching it how to cure cancer all on its own. Because not everyone who received the therapy responded to it, we are writing better instructions so that more patients will have better results. In this proposal, we hope to test these new and improved instructions in mice and see if they can cure cancer. Overall, if this work is successful, we will have discovered a new approach to treating cancers that we can then test in humans.
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