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.
Funded with support from the Scott Hamilton CARES Foundation
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.
Colorectal cancer is a leading cause of cancer death in the U.S. A major challenge in the treatment of cancer in general, and colorectal cancer specifically, is the ability of cancer cells to travel throughout the body and get into other organs. This means that we need medicine that attacks the cancer anywhere in the body. Cancer cells live with other types of cells that help it survive our medicines and let the cancer move around. The focus of my research is to make the cancer more susceptible to medication and less able to move around. This grant will test a new medicine that changes the blood vessels and cells that support the cancer. We will do a clinical trial adding this new medicine to the normal ones already used to treat colorectal cancer. This research will help find new treatments but also teach us more about the cells that support cancers and how to stop them.
Colon and rectal cancers are deadly diseases. The currently used treatments can improve the survival for patients, but new options are still needed. Some patients can benefit from drugs that speed up the body’s immune system against the cancer. Unfortunately, it is not currently clear which cancer patients are most likely to benefit from these treatments. Cancers can, in many ways, act like wounds that never heal. The scar tissue that forms around cancers contains important aspects that can prevent how your body’s immune system can see the cancer as abnormal. Additionally, in some cancers there are features that can actually stimulate the immune system. By better understanding these factors, we might be better able to identify which patients are most likely to benefit from these immune treatments. Also, understanding these processes can help make better immune drug combinations that can overcome these immune inhibiting factors. In this study, we first examine how these factors within the scars around cancer cells change the ability of the immune system to detect and enter cancers. Next, we look at which factors are associated with immune treatment response. Lastly, we study new treatments that might convert immune inhibiting cancer features to ones that stimulate the immune system.
Colorectal cancer is the second most common cause of cancer death. Immunotherapy is largely not effective in this disease. To work safely, it requires targets in tumors that are not also present in normal tissue. These are difficult to find. Our recent research shows that advanced colorectal cancers adopt a fetal-like state. This fetal-like state reactivates gene programs that are normally only expressed during early development. In normal adult tissues, these programs are turned off. This may make advanced cancer vulnerable. Reactivated fetal proteins could potentially be used as targets for new immunotherapies. Here we propose to study how these fetal proteins are recognized by the immune system. For this, we will use our unique and extensive biobank of organoids. Organoids are 3D cultures of cancer cells derived directly from patient tumors and normal cells. They are a more informative and realistic model of cancer than traditional cell cultures. We must first understand which molecules are shown to the immune system in cancer cells. We will then look for immune cells in the blood of colorectal cancer patients that can recognize the fetal molecules. This approach will ultimately lead to novel immunotherapies. These could help treat advanced colorectal cancer and related solid tumors.
Funded by Constellation Brands Gold Network Distributors
One of the most common kidney cancer syndromes is called HLRCC. Individuals with HLRCC are at risk for developing highly lethal kidney cancer, painful skin tumors, and fibroids. Better cancer prevention and treatment strategies are needed for HLRCC patients. HLRCC is caused by a mutation in a gene involved in metabolism. We found that the tumors that form in HLRCC patients have a unique metabolism that is reliant on the purine salvage pathway. Medicines have already been developed to block the purine salvage pathway, and one such medication, called 6MP, is currently used to treat patients with other types of cancer or autoimmune diseases. We found that HLRCC tumors are highly sensitive to 6MP treatment, and now propose to conduct a Phase 1 clinical trial to test safety and dosing of 6MP in HLRCC patients. We also propose to examine ways to prevent kidney cancer formation in HLRCC patients. This proposed research could have a huge impact on the lives of HLRCC patients through enabling clinical translation of a promising approach to treat their cancer and reveal effective cancer prevention strategies in this vulnerable patient population.
Fifty percent of people with Lynch Syndrome–related mutations will develop colon cancer. Over the last few years, we have started to understand that the immune system plays an important role in fighting colon cancer in Lynch Syndrome. The immune system is an army that protects us from cancer. In our project, we want to measure the strength of this immune army in patients that carry the Lynch mutation. We hope that these measurements will tell us who is at risk of developing cancer and minimizing the uncertainty of patients. Our goal is to study the immune system of patients that carry Lynch mutations in order to develop laboratory tests that one day can be used to predict which patients have a higher risk of developing colon cancer. At the same time, we hope that by studying a patients immune system we can understand the types of cells that are needed to fight cancer, and ways to develop new immune treatments to prevent cancer.
Brain cancers are typically fatal, even when patients undergo intensive treatment. While treatments have recently improved for many cancers, the last major treatment advance for glioblastoma (the most common aggressive brain cancer) was decades ago. Our research team is taking a new approach. We have discovered that aggressive brain cancers like glioblastoma often steal nutrients from the rest of the body. In this V Foundation-supported work, we will discover how brain cancers use these nutrients and whether blocking this nutrient uptake will slow brain cancer growth and improve treatment responses.
Multiple myeloma (MM) is a type of bone marrow (BM) cancer that remains a significant challenge to treat, despite therapy advancements. In this study, we aim to explore a new approach to enhance the effectiveness of standard MM treatments. Our focus is on a specific type of immune cells called myeloid cells, that play a role in tumor growth and immune evasion in MM patients. We observed that MM patients have an increase of a particular type of myeloid cell that express on their surface, a molecule called CXCR2, in the BM and places where the cancer has spread to bone: (osteolytic lesions). The myeloid cells may contribute to MM resistance to treatment and to evasion of the body’s immune system. Based on these findings, we propose a clinical trial to test a drug called SX-682, which targets CXCR2-positive myeloid cells. We will investigate whether adding SX-682 to standard MM treatment will improve patient outcomes. Our trial will focus on MM patients whose cancer has come back after initial treatment. The primary goal of our study is to assess the safety and tolerability of SX-682 with standard MM treatment. Additionally, we aim to understand how SX-682 affects the immune environment within the tumor and in the blood. By targeting CXCR2-positive myeloid cells, we hope to enhance the body’s ability to fight MM, improving patient survival. Our study represents a promising step towards developing more effective therapies for MM by harnessing the body’s immune system to better combat this challenging cancer.
