Translational Archives - Page 2 of 30

Kristy Brown, PhD

Women with excess body weight are more likely to get breast cancer than women with a healthy weight. The effect of excess body weight is especially harmful to women with a family history of breast cancer. Excess body weight can cause many harmful effects to cells. By limiting or reversing these changes, we may be able to prevent breast cancer. We think that exercise or weight loss can decrease the risk of breast cancer by reducing damage to cells. This is very important as it may provide options for women who decide not to get prevention surgery. In the future, we will apply what we have learned to a clinical trial.

Katerina Politi, PhD

In honor of Katie McDonald*

Lung cancer is the leading cause of cancer death worldwide and deeply affects many families. Twenty years ago, the discovery of mutations in the Epidermal Growth Factor Receptor (EGFR) gene and therapies that were effective for these tumors (targeted therapies) transformed the field and the lives of patients with this disease. This remarkable progress resulting from targeted therapies is countered by the fact that metastatic EGFR-driven lung cancer remains incurable due to the emergence of drug resistance. Therefore, there is an urgent need to improve treatment of EGFR-driven lung cancer so people live longer and ultimately cure the disease. Through our studies we have found new possible drug targets in this disease. In this proposal, we plan to understand whether these are new targets and how they work. We will also test drugs that have been developed against these targets in mouse and human models of EGFR-driven lung cancer. These studies will allow us to develop the foundation for designing a clinical trial for patients with EGFR-driven lung cancer with the goal of finding better ways of preventing and/or overcoming drug resistance and improving and extending the lives of people living with this disease.

Tullia Bruno, PhD

We aim to stop suffering and deaths from ovarian cancer. Therefore, we will explore how to improve the immune system’s ability to fight cancer. Cancer forms when normal cells change and grow wildly. The immune system can destroy abnormal cells. But cancer cells often evade immune system attacks. Ovarian cancer is a challenge. Only 10% of patients improve or survive with current treatments that help the immune system fight cancer. We study immune cells (B cells) and “neighborhoods” (tertiary lymphoid structures, or TLS) where these cells live. TLS can organize immune cells to fight cancer, and we investigate factors in ovarian cancer that impact TLS. We will test how immune cells (B cells) and non-immune cells (stromal cells) affect TLS creation and function. Our studies will show new ways to fight ovarian cancer. We will develop and lead new clinical trials. We will be poised to test a treatment for patients within five years that could change lives.

Rina Plattner, PhD

The number of melanoma cases in the United States continues to rise. When melanoma spreads to other organs, it is very deadly. Patients with this disease are usually first treated with medicines that help the immune system fight the cancer. This treatment works well for some people, but many can’t take the drugs because they have too many side-effects or simply do not work. For others, the medicines shrink the melanomas at first, but then they grow back. When immune medicines stop working, people with some kinds of melanomas can take other medicines(targeted drugs). However, targeted drugs do not work for a type of melanoma called NRAS mutant, which is very deadly and hard to treat. We found that a medicine used to treat leukemia may help targeted drugs work better for patients with this type of melanoma. In this proposal, we will learn how and why the leukemia medicine helps the targeted drugs work. We also will test our FDA-approved leukemia drug together with two different targeted drugs in mice. If the drugs work together to shrink the melanomas, then, in the future, we will test the treatment in patients by starting a clinical trial. Through this work, our goal is to give these patients more time to spend with their families, and eventually find a cure for this terrible disease.

Jennifer Rosenbluth, MD, PhD

Funded with support from Hockey Fights Cancer powered by the V Foundation presented by AstraZeneca

A recent study showed that short-term, low-dose therapy can provide lasting protection from cancer. Yet only two drugs are approved for breast cancer prevention in the US. One reason is the lack of clear signs that show a risk-reduction therapy is working. One possible sign is background enhancement on breast MRI. A higher level means a higher risk of getting breast cancer. When a patient lowers their risk by taking tamoxifen, the background also goes down. For others, it does not. This shows that the therapy is not working. We studied breast tissue to understand the reason for this background. We found that those with high levels had either high estrogen or signs of inflammation. In our new study, we will use tissue pieces from patients starting tamoxifen. Our goal is to find a molecular signal that shows the drug is working. For those who do not respond, we will test drugs that target inflammation. Finally, we will see if different background signals point to estrogen or inflammation. These signals could be assessed in a clinical trial at UCSF to support a personalized cancer prevention strategy.

Xin Zhou, PhD

This project is about making a type of cancer treatments called antibody-drug conjugates, or ADCs. ADCs are protein-based therapies designed like guided missles. They carry strong cancer-fighting drugs and deliver them directly to cancer cells using antibodies. But in many cases, the drug doesn’t get inside the cancer cell well enough, so the treatment doesn’t work as well as it could. We are trying to solve this problem by using a special feature on the surface of cancer cells called an internalizing receptor. This is a protein that acts like a fast-moving doorway—it pulls things inside the cell quickly. By connecting the drug to an antibody that targets this fast moving receptor, we hope to get more of the medicine inside the cancer cell, where it can do its job. We are focusing on two hard-to-treat cancers: triple-negative breast cancer and some types of lung cancer. We will test our new treatment in the lab and in models of these cancers. We will also study large research databases to learn which types of tumors might respond best. This research matters because many people with cancer still don’t have good treatment options. If this new approach works, it could lead to more effective and more targeted cancer treatments. It may help more patients benefit from ADCs, especially those with cancers that don’t respond well to current therapies.

Andrew Koh, MD

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.

M. Kohler, MD, PhD

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.

Michael Andreeff, MD, PhD

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.

Alex Kentsis, MD, PhD

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.