Grant Archive - Page 3 of 143

Benjamin Izar, MD, PhD

Cancer cells often live in a state of genetic chaos. This makes them hard to kill with existing drugs and allows cancer to spread to other parts of the body. We wanted to find out why this happens so we could stop it. We discovered that this chaos helps cancer cells hide from the body’s immune system. Usually, the immune system finds and kills cancer cells, but these cells stay invisible. To fix this, we created a new medicine. It targets the chaotic cancer cells but does not affect healthy cells. This drug turns the cancer against itself. Instead of hiding from the immune system, the cancer cells now send out a signal. This signal tells the immune system to come and destroy them. We are now testing this new medication on different types of cancers that are otherwise difficult to treat. If it works, it could lead to new treatments that save many lives.

Denis Guttridge, Phd

Cac Patients with cancer suffer from weight loss. This loss is due to the loss in skeletal muscle. Patients with cancer are vulnerable to muscle loss. Patients with muscle loss also respond poorly to their treatment which lowers their survival. There is no cure for muscle loss in cancer. Therefore, understanding the causes of muscle loss may lead to new therapies. Our laboratory studies how cancer promotes muscle loss. In this proposal, we identify an inflammatory factor. Our goal is to determine how this factor causes muscle loss. Importantly, this same factor also promotes cancer. Thus, our studies might understand how this factor functions in both cancer and muscle loss.

Grant Challen, PhD

Our research tries to understand the very earliest stages of blood cancer formation. The goal of this project is to use the processes by which these initial cells use to become cancer against them to develop a new treatments. In our study of the earliest stages of blood cancer development, our research has identified one way these cancer-forming cells are to live much longer than normal cells, which contributes to their increased growth in the bone marrow. We have identified a specific process these cancer forming cells use to live much longer than normal. This discovery is important because it opens up a new treatments. There is a drug that inhibits the same specific process we show these early blood cancer cells use grow faster. In this project, we will use this drug in our experiments and on cells from blood cancer patients to determine if it can preferentially kill these cells compared to healthy bone marrow cells. Most blood cancers currently have no cures. Our goal is to bring new treatment options for these patients. Ultimately, we hope that such approaches can even be used for blood cancer prevention.

Michael Haffner, MD, PhD

All cells in the human body have the same DNA, but different types of cells do different jobs. This happens because cells follow extra instructions that tell them how to behave. These instructions are part of a system called epigenetics. One important epigenetic marker is called DNA methylation. It is a small chemical tag on DNA that helps cells work the right way.In many aggressive cancers, large parts of the DNA lose these chemical tags. When this happens, the cancer often grows faster and is harder to treat. Until now, we have not known how to use this information to help choose better treatments.We found that cancers with low DNA methylation have a weakness. Their cells depend strongly on a growth signal called AKT to survive. Drugs that block AKT can slow down or kill these cancer cells. When AKT is blocked, the cancer cells become even more dependent on another system called PRC2, which helps control which genes are turned on or off. By blocking both AKT and PRC2 at the same time, we were able to kill cancer cells much more effectively.Based on these results, we believe low DNA methylation can be used to provide a clue that helps choose the best treatment. We plan to test drug combinations in a clinical study and develop simple tests to see how well the treatment works. If successful, this approach could lead to a more personalized treatment for patients with cancer.

Paula Pohlmann, MD, MSc, PhD

Funded by the Cancer Vaccine Coalition (CVC)

The INTERCEPT‑HER2 study is testing a new vaccine for people with HER2‑positive breast cancer who have finished all standard treatments but still show tiny signs of cancer in their blood. These signs are called minimal residual disease (MRD). MRD cannot be seen on scans, but it can warn us that the cancer may return. Finding MRD gives doctors a chance to act earlier, when the cancer is very small and the immune system is still strong.The vaccine uses cancer proteins to train the immune system to find and attack cancer cells. Earlier studies showed that the vaccine is safe and can activate the immune system, so it may help stop the cancer from growing again. In this study, 45 patients who test positive for MRD in the blood will receive three monthly vaccine doses and then two booster shots. They will also have regular blood tests for up to three years to see if the cancer signals in their blood go down or disappear.The main goals are to learn whether the vaccine can delay or prevent the cancer from coming back and whether it can clear MRD from the blood. The study will also show how often people with breast cancer still have MRD after treatment. Blood samples will help researchers understand how the immune system responds to the vaccine. What we learn may guide a larger future study and could lead to new ways to stop breast cancer earlier, before it becomes harder to treat.

Sidharth Puram, MD, PhD

Funded by the St. Louis Blues in support of Hockey Fights Cancer powered by the V Foundation

Tumors of the throat (called oropharynx carcinoma or OPC) are on the rise in the US and worldwide. Most of these are caused by a virus, called human papilloma virus (HPV). Current treatment of these tumors is fairly effective. As a result, researchers have been trying to reduce treatment to avoid side effects and problems with speech, swallow, and taste. But a portion of OPC patients do not have good outcomes. We are interested in identifying these patients before treatment begins so we can give them the right treatments. We found that some cancer cells turn off virus expression and this makes them treatment resistance and causes poor survival. In this study, we will use human models of OPC to understand what turns HPV expression on and off. We will also learn how different cancer cells with or without HPV talk with other cells in the tumor environment such as fibroblasts and immune cells.

Robert Bowman, PhD

Funded with support from Calhoun Associates
Abeloff V Scholar * (Tie for Top Rank)

Acute myeloid leukemia is an aggressive blood cancer. It affects thousands of people every year and often returns even after the newest targeted drugs. We have learned that, instead of dying, some cancer cells can “change their identity” to become a new blood cell type. These cells are called monocytes and they are able to escape therapy. This switch is like a costume change in a play: when the spotlight of treatment is on them, cancer cells put on a monocyte costume to hide. Later, when treatment eases, they can take off the disguise and return as cancer cells. We will test if these monocytes can turn back into cancer cells and cause disease to come back. We want to know how these cell changes happen and what helps them survive therapy. To answer these questions, we use new models that mimic patients’ cancer. We track how cancer cells looking at cell identity and genetic mutations. We also test new ways to block survival strategies, such as stopping the cells from becoming monocytes, in hopes of making current treatments work better and longer. By understanding and blocking the ways cancer escapes treatment, our goal is to develop strategies that keep patients in remission and improve survival.

William Hwang, MD, PhD

Abeloff V Scholar * (Tie for Top Rank)

Pancreatic cancer is one of the deadliest cancers. A condition called pancreatitis, which is prolonged inflammation of the pancreas, increases the risk of getting this cancer. For over 100 years, scientists have known that both pancreatitis and pancreatic cancer involve many nerves. But only recently have we started to learn that these nerves may actively cause pain, increase inflammation, and help cancer grow through direct interactions with cancer cells but also indirect effects on the immune system. However, we still do not fully understand how this works, and there are no treatments yet that target these harmful nerve-cancer interactions.Our research focuses on a type of nerve cell called a nociceptor. These nerves sense pain and use a protein called Nav1.8 to send signals. A new drug that blocks Nav1.8 was recently shown to be safe and helpful in reducing pain after surgery. In our project, we will test whether blocking Nav1.8 can also reduce pancreatic inflammation and slow cancer growth. We will also study how damaged nerves affect the immune system. Our early data suggests that injured nerves can change certain immune cells called macrophages, causing them to block T cells from attacking the tumor. Our overarching goal is to find new ways to prevent and treat pancreatic cancer by targeting the nerves that drive pain and disease. We hope these treatments will ease pain, stop cancer from forming or growing, and help patients live longer.

Maria Figueroa, MD

Funded in partnership with the Dolphins Cancer Challenge (DCC)

Chronic myelomonocytic leukemia (CMML) is a form of cancer of the blood in which malignant cells multiply very fast and accumulate, leaving no room for healthy cells to grow. This rare form of cancer does not respond well to current available treatments, leaving the majority of patients with very few options to find a cure. Even for patients who do respond to the treatments, the disease quickly comes back so that, overall, less than 20% of patients survive more than 5 years after the disease is first found. In our recent work, we studied a large group of CMML patients and analyzed their disease. We found that patients who did not respond to treatment all shared the presence of a gene known as PRAME, yet patients who did better never had this gene present. Very little is known about PRAME’s role in cancer cells in general and CMML in particular. Recently, new treatments have been developed that specifically kill cells with PRAME. While these new treatments are being studied in other cancers, their impact on CMML is unknown. Therefore, we will test whether these new approaches may be used for patients with this aggressive form of leukemia.

Amanda Dann, MD

Sarcomas are very rare types of cancer that develop from soft tissues- things like muscle, fat, and bone. Because they are so rare, they are often not caught early and have spread to other parts of the body by the time they are diagnosed. Once this happens, they can be very hard to treat. Our existing drugs often do not work very well to shrink or eliminate the cancer. My lab is working to develop new treatments for sarcoma, focused on targeting the nutrients these tumors need to grow and spread. Fast-growing tumors like sarcomas require more, and often different, nutrients than the normal tissues around them. This allows us to use drugs that target these pathways to slow down or shrink tumors while minimizing side effects to healthy tissue. We are able to measure how nutrients are used in patient tumors and using these findings to help refine treatment strategies. We have shown that sarcomas seem to rely heavily on certain nutrients- such as the amino acid glutamine, an important building block for many important cell functions. We are studying how new drugs that block the ability of cancer cells to use glutamine can be used to treat sarcoma. The goal of this work is to develop new treatments to help improve the lives of patients with sarcoma.