The Cancer Epigenetics (CE) research program, co-led by Ramin Shiekhattar, PhD and Maria Figueroa, MD, aims to incorporate basic and clinical research in the field of cancer epigenetics, taking into account the diverse needs present within Sylvester’s catchment area, and to pinpoint epigenetic factors that contribute to cancer risk, initiation, progression, and treatment response. To achieve these objectives, the CE Program encompasses three predominant aims: 1) Elucidate the functional roles of epigenetic regulators that are recurrently mutated in cancer initiation, maintenance, and progression; 2) Define the mechanisms by which oncogenic signaling pathways (e.g., mitogen-activated protein kinase) impinge on chromatin to alter transcriptional responsiveness; and 3) Validate epigenetic targets for therapeutic intervention and biomarker development in pre-clinical and clinical studies.

Sylvester stresses team science throughout the center as well as in its research programs. The CE Co-leaders constantly reinforce the program’s commitment to collaborative work by fostering an environment and program activities to encourage interactions among its members as well as with TB and CC members and investigators from other institutions.

Utilizing funds from The Pap Corps, the CE research program has continued to support the ongoing research of Feng-Chung Yang, MD, PhD who was awarded a Faculty Program Pilot Fund Award. The purpose of this award is to provide funding that will allow Dr. Yang to focus her efforts towards the development of an ASXL2 mouse model. ASXL2 mutations are found in 23% of t(8;21) AML and the cumulative incidence of relapse is higher in ASXL2 mutated t(8;21) AML. This clinical data suggests an important role of ASXL2 in the progression and/or the chemosensitivity of patients with this myeloid malignancy. Using these mouse models, will allow her to perform a series of experiments to determine the impact of ASXL2 truncation mutations on hematopoietic stem/progenitor cell behavior and its effect on the development of myeloid malignancies in mice. Establishing these mouse models will add great value to the R01 proposal she plans on submitting within the next year.

In addition, the funds allocated by The Pap Corps, have supported the research of Lluis Morey, PhD, Research Assistant Professor for the Department of Human Genetics. Dr. Morey’s lab studies the role of Polycomb proteins in stem cells and cancer. Their main goal is to understand how Polycomb proteins regulate embryonic stem cell pluripotency and differentiation, and how deregulation of Polycomb gene function affects oncogenesis and metastasis. Their studies include the use of genome-wide approaches, genome-editing and mouse models.

As further evidence of The Pap Corps Funds being used to support rising stars, Dr. Morey’s was recently selected as an awardee of the ACS Institutional Research grant for his proposal entitled, “Functional Crosstalk between Epigenetics and Estrogen in ER plus Breast Cancer.” The ACS extramural grants program seeks to support innovative cancer research across a wide range of disciplines to meet critically important needs in the control of cancer. These awards are considered seed money for newly independent investigators to initiate research projects.

The objective of the Cancer Control (CC) research program, co-led by Frank J. Penedo, PhD and Erin Kobetz, PhD, MPH, is to advance the science of cancer control, particularly for the diverse communities that comprise South Florida, Sylvester’s catchment area. This endeavor is strategically aligned with the program’s two specific aims: 1) Identify and characterize multilevel determinants of cancer etiology, risk and outcomes from prevention to survivorship among diverse populations; and 2) Design and test innovative interventions to reduce cancer disparities and improve outcomes from prevention to survivorship.

History

The funds allocated to Pediatric Cancer have helped support Dr. Julio C. Barredo, Professor for the Department of Pediatrics, in order to enable him to continue doing research that focuses on the molecular mechanisms leading to cancer cell sensitivity and resistance to conventional chemotherapy and molecular targeted agents. Using childhood acute lymphoblastic leukemia as a model, his laboratory has studied the molecular mechanisms that determine the cytotoxicity of methotrexate (MTX), a universal component of childhood acute lymphocytic leukemia (ALL) therapy. Acute lymphocytic leukemia is one of the most common childhood cancers.

Project Update for FY18

Dr. Barredo has focused his efforts around improving the outcomes of children diagnosed with ALL. The U.S. reports 6500 children diagnosed each year with this disease, with a cure rate of 90 percent with the right treatment. In contrast, Dr. Barredo found that out of the 700 children diagnosed each year in Peru only had a 40 percent cure rate. This was not due to a lack of doctors who specialize in treating such disease, but due to the fact that a majority the Peruvian children who develop ALL live in remote areas outside of Lima where these doctors reside. In other circumstances those that are able to travel to Lima, the hospitals often have no available beds or if there is a bed at one of the hospitals, it may have run out of the chemotherapy drug needed for the child’s treatment. Knowing this, Dr. Barredo made every effort to formalize a plan with Peru’s Ministry of Health. After several attempts to convince the previous Ministry of Health that these issues needed to be address, Dr. Barredo was selected to be part of the Peruvian Ministry of Health’s advisory team to tackle a variety of health issues. Through this assembly, he was able to develop a comprehensive plan that was implemented last year. With ALL being highly curable, it is projected to see results within the next three to five years. Cure rates will be dependent on all the doctors following the same treatment guidelines.

In addition, Dr. Barredo was also awarded, in December of 2017, a Pediatric Cancer Grant Award from the St. Baldrick’s Foundation for his innovative research to support childhood cancer research. Because these patients are of childbearing age, they often face decisions around egg harvesting, sperm collection, and embryo banking. With this award he will be able to jump start the only program of its kind in South Florida that provides key services to a patient population, age 15-39, with specific needs, such as oncofertility services, financial and family counseling, psychological services and genetics counseling.

History

Glioblastoma Multiforme (GBM) is one of the fastest growing and most aggressive types of brain tumors in adults that is formed in the supportive tissue of the brain. Although not surgically curable, there is evidence that the more of the tumor that can be removed followed by radiation and chemotherapy, the better the prognosis. Despite this aggressive treatment, average survival of these patients remains dismal and only a very small percentage of patients survive five years.

Project Update for FY18

Researchers at Sylvester Comprehensive Cancer Center, including Ricardo J. Komotar, MD, Associate Professor of Neurological Surgery, have discovered a peripheral biomarker in human blood serum that can be used to detect the presence and progress of glioblastoma brain tumors before and after treatment. Their findings were recently published in an article entitled, “Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme,” in the Molecular Cancer journal. Although experimental therapies for GBM are in clinical trials, there is an urgent need for a peripheral GBM biomarker for measuring treatment response.

The funds allocated to GBM have helped support the research showing that HOTAIR levels are controlled by an epigenetic regulator named BRD4. This discovery has suggested that by monitoring the levels of HOTAIR during clinical trials it will enable researchers to determine whether BRD4 inhibitors are effective and in addition can help determine when, or whether, tumors return. As a part of the University of Miami Brain Tumor Initiative, several Sylvester researchers have received approval from the IRB to measure HOTAIR in GBM patients during treatment in order to determine when progression occurs.

History

Precision Medicine is a new method of approaching cancer care. Thanks to the advances in molecular testing, an individual patients’ tumor can be analyzed for unique biomarkers that can then direct therapy choices. These advances have precipitated the “Precision Medicine” approach to cancer care, where tumors are no longer treated according to their location, but rather to their unique biomarkers. This method has become mainstream, with the FDA issuing its first biomarker based approval in May of 2017. The American Society of Clinical Oncology (ASCO) recognized this topic as the most innovative and important topic by making Precision Medicine the theme of its 2018 Annual Meeting.

In 2015, the Community Foundation of Broward County made a financial commitment, conditioned upon a matching gift, to bring precision medicine to the area. The matching gift was made by The Pap Corps, Champions for Cancer Research. Both the Community Foundation of Broward County and The Pap Corps, Champions for Cancer Research, committed identical funding in 2016. The Community Foundation of Broward County has committed to renew their agreement through 2020.

Project Update for FY18

The Defining Platforms for Individualized Cancer Treatment (DePICT) study opened in the beginning of March 2016. Since then, we have assisted 180 patients in gaining access to molecular analysis. In support of the increased access to molecular testing, the Precision Medicine Molecular Tumor Board was established in March of 2016. The board is composed of a group of cancer experts who provide physicians with clinical management recommendations based on the patient’s individual tumor mutations. Through this mechanism, more than 300 patients have been reviewed and provided with personalized therapy options, including clinical trials. More than 25% of patients who are assessed through this mechanism have been able to continue to treatment using novel therapies.

In order to increase the participation of Broward and Palm Beach patients, we have enabled videoconferencing of the Precision Medicine Molecular Tumor Board meeting to the Plantation and Deerfield Beach satellite clinics. This has allowed the physicians throughout the tri-county area to participate in the meetings seamlessly, resulting in an increase of participation of physicians and patients.

As of March of 2017, with the support of the state of Florida via the Agency for Healthcare Administration, we have begun the implementation of a software system to streamline and automate this process so that every patient who undergoes molecular testing has access to the Molecular Tumor Board. We have completed the Phase I deployment of this software, and are continuing to the second Phase.

In addition to the National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial Sylvester has now opened a second major national Precision Medicine Trial. In February of 2017, the American Society of Clinical Oncology’s Targeted Agent and Profiling Utilization Registry (ASCO TAPUR) was opened at Sylvester. These trials allow patients access to a large portfolio of targeted therapies that are either experimental or not approved in their tumor type (off-label). The DePICT trial is working in conjunction with these studies to screen patients, and together we have treated more than 40 patients in the Miami, Plantation, and Deerfield Beach locations. This trial has been one of the highest accruing trials at the Deerfield Beach location, improving our ability to provide Palm Beach patients with cutting edge care closer to home.

Also, in 2017 The Pap Corps, Champions for Cancer Research Nurses has helped train and mentor new advanced practice nurses. This program has provided them an opportunity to delve into the complex clinical cases here at Sylvester and also develop practice change through quality initiatives identified during the fellowship. Studies have been done nationally identifying the importance of having transition-training programs for nurses that contribute to the care of a growing population of cancer patients by decreasing burnout, decreasing turnover and increasing return on investment. With the assistance of The Pap Corps, we were able to provide salary support for one nurse practitioner. Through this program the Nurse practitioner was able to meet all criteria for a successful completion.

Future Directions for FY19

Due to the successful opening of the DePICT studies at Sylvester in conjunction with the establishment of the Precision Medicine Molecular Tumor Board, Sylvester will be presenting the data collected from the Molecular Tumor Board at the American Association of Cancer Institute’s Clinical Research meeting in July of 2018. By leveraging the funds provided by The Pap Corps we plan to continue increasing the participation of the Broward and Palm Beach physicians and patients, via the available videoconferencing of the Precision Medicine Molecular Tumor Board meeting at the Plantation and Deerfield Beach satellite clinics.

The funds from The Pap Corps will help us bring live the Phase II process of the software system that will enable patient’s access to the Molecular Tumor Board. Additionally, we plan to implement an electronic test ordering system to ease the process for physicians to order advanced molecular testing. This will ensure that patients at all of the Sylvester sites have efficient access to testing.

The continued support of the Community Foundation of Broward and The Pap Corps allows the DePICT trial and the Precision Medicine Initiative at Sylvester to continue to grow and serve more patients. Funds distributed for FY19 will enable us to provide salary support of personnel, travel expenses related to the initiative, and supplies.