Michael Zinner, M.D.

Funded by Hooters of America, LLC

The healthcare landscape has dramatically changed in South Florida, and we welcome you to be a partner in this transformation. Miami Cancer Institute at Baptist Health South Florida opened its doors in 2016 and is now seeing nearly 1,000 patients per day. The Institute, supported by a clinical and research alliance with Memorial Sloan Kettering, one of the leading academic cancer centers in the world, grants our patients access to the most advanced clinical trials for breast cancer. Patient accrual remains a huge challenge in clinical research, and the grant will go towards supporting recruitment for the important studies which in many cases, may give patients access to new therapies that are not yet readily available. The Institute will be proactive with the creation of recruitment materials as part of a well-coordinated campaign to address all aspects of enrollment as well as presenting information in an easy to understand and honest way. It is our goal to track enrollment efforts and adjust accordingly to what works best for our patient base and the community we serve. The mission of the breast clinical trial enrollment program is to provide innovative, patient centered cancer care through access to cutting edge treatment.

Zhijie (Jason) Liu, Ph.D.

V Scholar Plus Award – extended funding for exceptional V Scholars

More than 40,000 American women die of breast cancer each year. One out of every eight women in the U.S. will develop invasive breast cancer during their lifetime. In 70% of these women, estrogen and estrogen receptor α (ERα) are key players in breast cancer diseases. Keeping this endocrine signaling function low by endocrine therapy is the best treatment right now. Yet, after 5 years, hormonal treatment stops working in more than 30% of these patients and the disease returns. Because hormone resistance is still a challenge, there are few effective therapies for these patients. We plan to study estrogen and ERα related to hormone resistance.

ERα binds DNA elements that regulate gene expression. These elements are very important in cancer development and progression. When these elements lose control, breast cancer becomes resistant to hormones. Thus, if we can find ways to understand and correct these elements in hormone resistant cells, we can find cures for ERα-positive breast cancers. The goal of this project is to understand how ERα controls DNA elements. We will identify markers to measure the presence and progression of breast cancer. Our research results may lead to new therapies that target this disease. Discoveries from this project may help with treating other cancers and may be useful for other research fields.

Yong Zhang, Ph.D.

V Scholar Plus Award – extended funding for exceptional V Scholars

Cancer cells contain a set of highly active proteins. They can add small groups to a series of target proteins. These uncommon additions are often linked with tumors found in breast, liver, and other tissues. To date, it is still unclear how those aberrant additions cause cancer. To answer this question, it is crucial to know all the interaction targets for the additions in cancer cells. But no method has been made available to resolve this key issueIn this project we are aimed to create an innovative platform to achieve this goalOur research plan will use chemistry and biotechnology to make new tools for target identification. A particular member in this group will be chosen for this work. Because it shows much higher activities in diverse types of cancerThe full range of interacting targets for this protein will be clearly determinedMoreover, the patterns and levels of such interactions in cancer cells can be precisely measured by our creative approach. These findings will unveil the interaction networks of this cancerous protein to guide our further studies. The fundamental knowledge obtained from this work will advance our understanding of cancerImportantly, it will foster the development of new approaches for cancer detection and treatment. 

Yuliya Pylayeva-Gupta, Ph.D.

V Scholar Plus Award – extended funding for exceptional V Scholars

Pancreatic cancer is a very aggressive disease. It is the 3rd leading cause of cancer deaths in the USA. Only 8% of patients who can undergo surgery will survive past five years. Late diagnosis and lack of good treatment options are some of the reasons for this outcome. Recent progress in cancer immune therapy showed effect in cancers such as relapsed leukemia and metastatic melanoma. Unfortunately, immune therapy was not effective in patients with pancreatic cancer. One explanation for this result is that pancreatic cancer blocks immune responses against cancer. Thus, understanding how cancer promotes immune suppression is vital to our ability to treat this deadly disease. Our initial work has revealed that B cells promote growth of pancreatic cancer and resistance to immunotherapy. However, it is not clear how B cells promote cancer growth, and how targeting these cells can benefit patients. We propose to understand how B cells function in pancreatic cancer. The goal of this research project is to find new targets that can block immune suppression in pancreatic cancer. Using both mouse models of pancreatic cancer and patient samples, we hope to identify B cell based targets in pancreatic cancer. We ultimately hope to translate our findings into effective therapies that may also work with existing immune therapy treatments.

Aniruddha Deshpande, Ph.D.

V Scholar Plus Award – extended funding for exceptional V Scholars

Cure rates for childhood leukemia have considerably improved in the last few years. Despite this, there are certain sub-sets of leukemia that do not respond well to current therapies. Currently used treatments are often extremely aggressive and non-specific, leading to significant debilitating effects in these patients. The overall objective of this application is to validate exciting new therapeutic targets that we have identified in high-risk subsets of AML using genetic and chemical approaches. 

Michael Kastan, M.D., Ph.D.

The Duke Cancer Institute and the College of Veterinary Medicine at N.C. State University formed a Comparative Oncology Consortium (COC), taking advantage of their expertise and national leadership in their respective disciplines and their geographic proximity. The goals are to collaborate in pre-clinical and clinical cancer research activities in order to advance our understanding of both cancer causation (a high incidence of specific cancers in specific dog breeds provides opportunities to identify new cancer susceptibility genes and environmental factors in cancer causation) and of behaviors and genetics of specific tumor types, as well as to coordinate clinical trials in humans and canines so that novel therapies can be tested in both settings, with information gained in one setting informing the other. In addition to response outcomes of these cancer therapies, the ability to use biomarkers and pharmacology in the canine models can be a novel addition to the characterization of these new cancer therapies and these insights could result in significant enhancements of clinical trial designs (including dosing, scheduling, and combination therapies) when these treatments are tested in human clinical trials. Cost savings and improved clinical trials design would help encourage pharmaceutical companies to use the canine models as part of the assessment process and would benefit the canine patients by giving them access to these novel therapies.

Hatem Soliman, M.D.

Funded by Hooters of America, LLC

Only a small percentage of patients with cancer in the US enroll on to clinical trials. This is creating a bottleneck for the development of new treatments. Efforts to improve how patients are identified for clinical trials are important to overcome this problem. One such effort which is showing promise is to use an individual known as a “pre-screener” to aid the clinical team in identifying eligible patients. The pre-screener functions as an extra set of eyes to review information generated from our electronic medical record as their records come in from referring physicians. They will be trained to look for patients meeting certain eligibility criteria and then notify the clinical team about the matches ahead of their visit. This will allow the team to better prepare and notify the coordinator for the study to be available at that time. The pre-screener will also serve as a resource for patients using our clinical trial education center in the clinic waiting area to help them navigate through the available information to identify a potential trial option to discuss with their physician during their visit.

James Brugarolas, M.D., Ph.D.

Immunotherapy has revolutionized cancer treatment. Immunotherapy drugs work with the immune system, which normally fights intruders such as viruses, to kill cancer cells. One approach involves taking down defenses set up by cancer cells to escape immune cells. Some tumors, such as kidney cancer, melanoma, and lung cancer, display on their surface a protein (PD-L1) that shuts off approaching killer immune cells. Drugs have been developed that mask PD-L1 allowing killer cells to dispose of cancer cells. Discoveries underlying these developments were recognized with a Nobel Prize in 2018.

However, not all tumors use the same defense mechanism. Here, we propose a novel strategy to identify patients most likely to benefit from drugs masking PD-L1. Up until now, most approaches have focused on evaluating PD-L1 on tumor biopsy samples. However, only one cancer site is sampled, few cells are evaluated, and the results are often unreliable.

We have developed a strategy adapting a radiology test, positron emission tomography (PET), and a PD-L1 masking drug, that allows us to evaluate PD-L1 across all tumor sites. In preliminary experiments, we show that we can label a PD-L1 masking drug so that it can be detected by PET. We then show, using patient tumors transplanted into mice, that we can identify tumors with high PD-L1.

Our goal is to evaluate immuno-PET (iPET) in patients in a clinical trial. If successful, iPET will better match patients to their immunotherapy drug, and identify patients unlikely to benefit and for whom other strategies should be developed.

Roger Lo, M.D., Ph.D.

RAS is a gene when mutated causes a wide variety of human cancers. However, there is no specific therapy against cancers driven by RAS mutations. Metastatic melanoma is an aggressive skin cancer, and up to a third of cases are caused by RAS mutations. In this study, we propose to develop a specific therapy against RAS mutated melanoma. This therapy involves starting with one drug that optimizes the patient’s own immune system against the cancer followed by adding on a second drug that blocks an overactive cancer-causing pathway driven by mutated RAS. We will first test this therapy in animal models in order to understand the mechanisms. We will then begin to design and initiate a clinical trial to test this regimen in patients whose melanoma harbor RAS mutations. Thus, we will test the hypothesis that distinct drugs when combined in a specific sequence may have dramatic anti-cancer effects not expected of individual drugs.

Sabine Mueller, M.D., Ph.D.

Funded by 2015 Wine Celebration Fund-A-Need

Children with diffuse midline gliomas continue to have a dismal prognosis and most children die within one year of their diagnosis. Decades of clinical research and hundreds of clinical trials have not been able to change the outcome for these patients. Studies have shown that the majority of these tumors carry a specific mutation referred to as H3.3K27M which is present in almost all tumors cells making this a very attractive target for immunotherapy approaches.

Within this proposal we are aiming to assess the benefit of a specific immunotherapy approach referred to as T cell receptor approach. We have been able to show in the laboratory that this approach is able to kill H3.3K27M tumor cells very effectively. Based on our exciting animal data, we propose to test this new therapy approach in clinic. Subjects whose tumors carry the H3.3K27M will undergo collection of their own T-cells prior to start of radiation therapy, which is considered the standard of care for these tumors. These T cells will subsequently be modified in the laboratory to specifically recognize the specific H3.3K27M mutation. These modified T cells will then be given back to subjects once they completed radiation therapy.

Within this project we will assess if such a therapy approach is feasible and safe. This project has the potential to significantly impact the treatment approach for a disease for which we have not achieved any improvement for the last several decades and is the first of its kind for this devastating disease.

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