Funded by the Dick Vitale Pediatric Cancer Research Fund
Acute Lymphoblastic Leukemia (ALL) is a common cancer in kids. There are two types, B-ALL and T-ALL, depending on the type of white blood cells affected. Most kids get better with current treatments, but sometimes the cancer comes back and we can’t help them anymore. That’s why we need new treatments for T-ALL.
We know that certain drugs used in the hospital affect how leukemia metabolism works. So, we wondered if changing the diet could also help. In our lab, we tried different diets on mice with leukemia. Surprisingly, we found that removing just one component of the food (an amino acid), made a big difference. Leukemic mice eating food without this amino acid lived much longer.
Now we want to understand why this dietary approach helps and if we can use it in combination with other treatments. We will study mice with leukemia and samples from real patients to see how this amino acid affects cancer. We also want to find out if combining this diet with current treatments works even better.
If our research is successful, we can try it on real patients. We want to see if reducing this amino acid in the diet can make treatments safer and help more kids survive, especially those whose cancer has come back. This research is important because it could give us new ways to treat leukemia and help more kids get better. It might even help with other types of cancer too.
Acute Myeloid Leukemia (AML) is the most common and deadliest blood cancer in adults. In 2022, over 11,000 AML patients sadly lost their lives in the USA. The treatment options for AML have stayed the same for many years. But in 2018, a new oral medication called Venetoclax was introduced as a potential breakthrough for AML treatment.
Normally, when our cells become damaged, they have a way of self-destructing called apoptosis. It helps stop any defects from spreading in our bodies. Unfortunately, cancer cells, including those in AML, don’t follow this program and become “immortal,” spreading and causing trouble. Venetoclax is designed to make those cancer cells self-destruct, specifically targeting and killing them.
At first, AML patients showed promising responses to Venetoclax. However, it’s disheartening that about 3 out of 10 patients don’t respond to the medication and in many other patients, AML comes back after treatment. That’s where our research comes in. We want to understand why some patients don’t respond to Venetoclax and how leukemia cells manage to escape apoptosis triggered by the medication.
Through our studies focusing on the molecular aspects of resistance to Venetoclax, we aim to identify potential targets for new and improved therapies for AML. Our studies will also propose combination treatments that could enhance the effectiveness of Venetoclax. Ultimately, with the knowledge gained from this research, we aspire to lay the groundwork for future clinical trials and develop better and safer treatments that will help AML patients live longer and have better lives.
Invasive ovarian cancer is one of the deadliest types of cancer in the world, as less than 30% of these patients remain alive after 5 years. Treatment options are limited for these women, as they usually do not respond well to a new type of therapy that uses the patient’s own immune system to fight cancer. This is despite the fact that ovarian cancer does often have high numbers of T cells – an immune cell that has an ability to kill cancer cells. Therefore, identifying ways to improve the T cell’s ability to kill ovarian cancer cells will likely improve the outcome of these women. To this end, we have discovered a mutation in a molecule found in ovarian cancer cells that is associated with an improved outcome. Importantly, we have found the mutated version of this molecule is linked with increased T cell activity in ovarian cancer. Therefore, our study is designed to understand the connection between this molecule and immune cell activity. Our work will explain a new way that T cells in ovarian cancer can be stimulated to kill cancer cells and will improve our understanding of how immune activity is orchestrated in this disease. We expect that the completion of this work will drive the development of drugs that can target this molecule in cancer cells to improve responsiveness to ‘immune therapies’ and to significantly improve the outcome of women with ovarian cancer.
Funded in collaboration with ESPN
Black women have significantly higher breast cancer death rates compared to Non-Hispanic White women. This difference represents an important public health concern and an important target for the development of solutions. Cancer clinical trials are important in solving the differences that exist in cancer health care between Black and White patients, because they provide high-quality, guideline-driven health care. It is important to have clinical trial participants be similar to that of the general population, so that any development of new drugs or interventions from these clinical trials are effective for everyone in the population. Unfortunately, Black women are substantially underrepresented among cancer clinical trials. Consequently, given their lower participation, any positive outcomes from such trials may not be relevant to Black patients. If not corrected, this will lead to continued differences in cancer health care between Black and White patients. The most commonly identified barriers affecting participation in clinical trials among Blacks, include issues of trust, experimentation, poor communication, and access. These issues need to be addressed because, Black patients participate at similar rates compared with White patients when offered clinical trials and help with any barriers. We are part of the largest health system in the state of New Jersey and serve large populations of Black patients. We offer a variety of cancer clinical trials and we propose to put into action, a comprehensive program using patient navigators, patient advocates, marketing and communication, and physician engagement to increase awareness and participation of Black breast cancer patients in clinical trials.
Funded by the Constellation Gold Network Distributors
Pancreatic cancer is one of the deadliest cancer types in the world. Most pancreatic cancer patients already develop advanced disease and are not suitable for surgery. A very small number of patients can live longer than ten years after surgery and are referred to as long-term survivors. Recently, unique bacteria were found in tumors from long-term survivors but not patients with shorter survival. In addition, long-term survivors tend to have higher numbers of T cells in their tumors – a cell type that is central to the immune system. Therefore, T cells might induce more powerful immune responses against cancer in long-term survivors through these unique bacteria. More precisely, we think that T cells in long-term survivors might “see” antigens from the bacteria and at the same time similar antigens from cancer cells. Our study is designed to understand the T cell responses unique to long-term survivors through T cell specificity inferences with our computer algorithms. The specificity inference will further guide our effort in finding these antigens that are “seen” by T cells in long-term survivors. Identifying these antigens from both cancer cells and the unique bacteria in long-term survivors will help us invent new and better treatments for pancreatic cancer patients.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. CLL starts in the bone marrow in a type of white blood cells called B-lymphocytes. Standard chemotherapy has been successful in treating most patients, but drugs often are not effective when a small group of leukemia cells have specific changes in their DNA. In our earlier work, we used advanced DNA sequencing and found mutations that were present in only a few leukemia cells. These mutations, which were not found by common approaches in the clinic, changed the function of a gene called TP53. The cells that had these mutations became the major leukemia population when CLL came back. To treat such high-risk patients, new drugs have been developed, which disrupt the processes that leukemia cells use to interact with their environment. Similar to resistance against chemotherapy, some cells, which may have alterations that stop the drug from working, are not killed and can result in CLL’s return. In this project, Rutgers Cancer Institute of New Jersey and the Institute of Oncology Research will work together to analyze patient samples collected during treatment in a clinical trial, and apply highly sensitive experimental approaches to thousands of single leukemia cells to develop models that help us understand how CLL cells behave and change under new therapies. We will test our results in independent groups of patients who are being treated with the same drug, with the goal of finding new ways for doctors to diagnose and treat patients.
Funded by Marketing Research Consultants
In Memory of Mary Ann Ingoglia
Funded by Marketing Research Consultants
Funded by the UNICO Foundation
In memory of Len Sodini