Grant Archive - Page 2 of 143

Frank B. Furnari, PhD

A brain cancer called glioblastoma is one of the deadliest cancers. Even with surgery, radiation, and chemotherapy, most patients only live about 15 months. The biggest problem is that the cancer almost always comes back. Scientists are still learning why this happens. Some cancer cells, called “persister cells,” can survive radiation therapy by going into a kind of hibernation. When treatment stops, these cells wake up and start growing again, causing the tumor to return. Think of it like weeds in a garden. If you don’t remove all the roots, the weeds grow back.Our research discovered that a protein called BRD2 helps these persister cells survive radiation. When we remove BRD2 from cancer cells in the lab, they die from radiation. But when we use drugs to block BRD2, some cells still survive. They find other ways to stay alive.We’re now testing drug combinations. These drugs block both BRD2 and the backup routes cells use to survive, stopping cancer cells from returning after radiation. Another problem is getting drugs into the brain. The brain has a natural wall that blocks most medicines. We’re creating tiny particles that can carry drugs past this wall. Think of them as special delivery trucks that know a secret path into the brain. If this works, we could have new treatments that stop brain tumors from returning after radiation. This would give patients more time with their families, changing this deadly cancer into a disease we can control.

Justin Milner, PhD

Pancreatic cancer remains one of the most difficult cancers to treat. There is a clear need for more effective therapies. CAR-T cell therapy has shown promise in some cancers. However, pancreatic tumors create a harsh environment that weakens T cells and limits how they work. This project aims to reprogram T cells so they can persist and continue fighting in these conditions.T cells can be genetically engineered. This allows us to adjust the instructions that control how they behave. Most current approaches focus on removing barriers, like taking the brakes off. In this project, we take a different approach. We aim to strengthen T cells so they can better adapt and function within tumors.Our goal is to identify changes that make T cells more potent and longer-lasting. These insights will enable more effective CAR-T therapies for pancreatic cancer and other solid tumors.

Amit Verma, MD

Myelodysplastic syndromes (MDS) are a group of blood cancers that cause low blood cell counts. The most common problem is anemia, which means the body does not have enough red blood cells. This can make people feel very tired and often leads to the need for blood transfusions.In MDS, the bone marrow (where blood cells are made) shows higher levels of inflammation. The cells in the bone marrow produce proteins that increase this inflammation in the body. In this project, we aim to reduce inflammation by targeting a key system called the inflammasome. The inflammasome is a group of proteins that helps to produce a substance called IL-1beta, which can make the disease worse.We are studying a new drug called HT-6184 in our lab. This drug helps block the inflammasome and reduce inflammation. In early lab tests, it has lowered inflammation and increased red blood cell levels.In this study, we will first identify the proteins and cells that cause increased inflammation in MDS. Then, we will test ways to block these targets using antibodies and specific drugs in lab-grown cells and patient blood samples. Most importantly, we will test how well the inflammasome-blocking drug works in MDS blood samples and in mouse models of the disease. This drug has already been approved by the FDA for clinical trials.If our results are successful, this research could help move this drug quickly into clinical trials designed for patients with MDS.

Elsa Flores, PhD

Funded by the Stuart Scott Memorial Cancer Research Fund

Cancer happens when certain genes change and cells grow out of control. New efforts look closely at each patient’s tumor so researchers and doctors can pick treatments that shrink that tumor. This is important for finding ways to treat pathways that are hard to target with drugs. One of the hardest to fix is TP53 (also called p53), the gene most often changed in cancer. Because p53 helps normal cells work, trying to target it directly can cause harmful side effects. To get around that, our research studies two related genes, TP63 and TP73, which can do some of the same jobs as p53 to stop tumors from growing. Our earlier V Foundation funding in 2005 helped us discover new roles for TP63 and TP73, and now we plan to use the pathways they control to make up for lost p53 function. This idea may work better than trying to fix p53 directly, since those methods are often only partly effective or only work for certain mutations. We also found special non-coding RNAs that affect how tumors grow and respond to treatment. The new therapies we propose aim to target tumors precisely and cause less harm to patients. Although we focus on lung, breast, and ovarian cancers, these approaches could help any cancer with TP53 mutations.

Jeffrey Smith, MD, PhD

Funded by the Stuart Scott Memorial Cancer Research Fund

Prostate cancer risk runs in families. A man’s risk of prostate cancer roughly doubles for every close family member who has been affected. Men in the family also tend to share how aggressive the cancer is. For example, how long a father survives with the cancer is strongly predictive of a how long a son will survive with the cancer. Studies have uncovered genetic risk factors for prostate cancer that distinguish which men are at high risk. But these factors poorly predict disease course. Two separate features of a cancer predict how aggressive it will be. These are 1) how abnormal the cancer cells are and 2) extent of cancer spread. Using such clinical features, two-thirds of cases are thought to be less aggressive and follow a watch-and-wait strategy. But over half advance and require active treatment. Ability to better recognize the path that the cancer is likely to take is needed. This is a study to discover the factors passed down in families that guide this path. The study also tests whether these factors predict which men followed by watch-and-wait will advance and require treatment.

Michelle Ozbun, PhD

HPV is a very common virus. Most of the time, the body clears it on its own. But sometimes HPV sticks around and causes abnormal cells to grow in the cervix, anus, genitals, or throat. If those abnormal cells aren’t caught and treated, they can turn into cancer.Right now, getting treated usually means clinic visits, special tests, and sometimes painful procedures to remove the abnormal cells. For people in rural areas, Native communities, or places without good healthcare access, that’s a real barrier. People living with HIV face even higher risk because their bodies have a harder time fighting off HPV.This means people who already have the least access to care are the most likely to develop cancers that could have been prevented.Researchers are working on a treatment that people could use at home — an antiviral that someone would apply themselves, without needing a clinic visit. Combined with at-home HPV testing and follow-up through telehealth or community health workers, this approach could make it much easier for people to get treated early.For patients, that could mean fewer procedures, less time away from work, less travel, and less of the stress that comes with waiting and worrying.The bigger goal is simple: if treatment is easier to get, more people will get it — and fewer people will develop cancer.

Christian Hinrichs, MD

Funded by the Stuart Scott Memorial Cancer Research Fund

Cancers caused by human papillomavirus (HPV), like cervical and throat cancers, are hard to treat once they spread. Our team developed a new approach called TCR-T therapy to fight HPV cancers. We take a patient’s own immune cells, called T cells, and modify the T cells in a lab so they can recognize cancer cells. After growing the cells for several weeks, we put them back into the patient. Think of it as programming T cells with a lock-and-key that fits only HPV cancer cells, allowing them to find and destroy tumors. In a clinical trial, two patients with advanced cancer saw their tumors disappear after a single treatment, and they have remained cancer-free for over a year. While successful, TCR-T therapy is slow and expensive because it must be custom-made for each patient. Some patients with fast-growing tumors simply cannot wait, and some hospitals cannot afford to offer the treatment. To solve this, we are developing a simpler treatment called a T cell engager. This protein works like double-sided tape: one side attaches to the cancer cell and the other to a T cell. By pulling the cells together, the immune system can attack the cancer. Because these proteins can be mass-produced and stored, treatment could become faster, cheaper, and more widely available. Our goal is to advance T cell engagers through lab testing and into clinical trials so more people with HPV cancers achieve lasting remission.

Natalie Silver, MD, MS, FACS

Anaplastic thyroid cancer (ATC) is a very dangerous type of cancer. Most people with this cancer only live a few months after doctors find it. The medicines we have now don’t work well. Sometimes the tumors get smaller at first, but the cancer almost always comes back. We need better ways to treat this disease.ATC is hard to treat because it tricks the body’s defense system. Our body has special cells that are supposed to fight cancer. But this cancer confuses some of these cells and stops them from attacking. When this happens, your body can’t fight back against the cancer. This study tests a brand-new way to treat cancer. Doctors take a small piece of each patient’s tumor and use it to make a special medicine just for that person. The medicine is packaged into tiny particles (called RNA-LPAs). These particles are designed to wake up the body’s defense system and teach it to find and attack the cancer. This treatment has never been tested on people with ATC before.In this early clinical test, patients will get the new treatment while doctors carefully check to make sure it’s safe. Doctors will collect blood and tumor samples to see if the body’s defense system is responding. This helps scientists learn if the treatment is working the way they hoped. If this works, it could help patients with ATC live longer. It might also help doctors treat other types of cancer that don’t respond to today’s medicines.

Andrew Lane, MD, PhD

Acute myeloid leukemia (AML) is a fast-growing blood cancer that is hard to cure. Even with today’s treatments, fewer than 1 in 5 people are alive five years after they are diagnosed. Many patients do well at first and are told they are in “complete remission,” which means doctors cannot find cancer with standard tests. But the cancer often comes back.This happens because a small number of leukemia cells survive treatment. These are called minimal, or measurable, residual disease (MRD). MRD cells are hard to find and hard to destroy. They can hide in the body, resist drugs, or change over time. Doctors are getting better at finding MRD, but we still do not fully understand why these cells survive or how they are different from the original cancer.This project aims to learn what makes MRD cells different and how to target them. Our early work shows that MRD is not just a smaller amount of leukemia—these cells act differently and depend on certain survival pathways. We have collected samples from more than 120 AML patients at different stages: diagnosis, remission, and relapse. Using advanced tools, we will study these cells closely to find new treatment targets. Our goal is to develop better treatments that remove MRD, stop the cancer from coming back, and help more patients stay in remission and be cured.

Trudy Oliver, PhD

Some cancers are very hard to treat because they grow fast and stop responding to therapy. One example is a group of tumors called tuft-like cancers. These cancers can form in several organs, including the lung. Patients with these tumors often have few treatment options, and the disease can progress quickly.Our research focuses on finding a new way to treat tuft-like cancers. Our lab discovered a drug target that appears to be very important for the survival of these cancer cells. Early studies show that blocking this target can slow tumor growth in laboratory models.This treatment may also help the body’s immune system fight cancer. In other words, hitting this target may deliver a “one-two punch.” The drug could weaken the tumor while also helping immune cells attack it.In this project, we will study how this target helps tuft-like cancers grow and survive. We will test drugs that block it in models that closely resemble human cancer. We will also study patient tumor samples to learn how these cancers interact with the immune system.Our goal is to move this discovery closer to clinical trials. If successful, this work could lead to the first targeted treatment for tuft-like cancers and give new hope to patients facing this aggressive cancer type.