Game-Changer Archives - Page 42 of 45

Nikhil Wagle, M.D. & Pingping Mao, Ph.D.

Funded in Collaboration With Stand Up To Cancer (SU2C)

Clinical oncology has entered an era of personalized molecular diagnosis and targeted therapy. This means treatments are tailored to each patient based her tumor’s histopathological and genetic characteristics. Such personalized treatment often involves a combination of multiple active agents to treat one tumor. In estrogen receptor positive (ER+) breast cancers, the three most promising classes of treatments are hormonal therapy, PI3K pathway inhibitors and cell cycle inhibitors.

Although patients derive benefit from such treatment, for most of the advanced ER+ breast cancers, the tumors respond initially but then stop responding, which is called “resistance” to therapy. Unfortunately, this resistance results in death in most cases of advanced breast cancer. Treating these cases requires developing novel therapeutic strategies to overcome the resistance based on an understanding of the mechanisms of resistance.

In this project, we leverage the leading edge technology of high-throughput whole-genome screening to discover mechanisms of resistance to each of three classes of drugs and all of their combinations. We also characterize the identified genes and their function in a variety of breast cancer cell types and mouse models. The knowledge of resistance to treatment obtained through this project will guide our effort to design more effective combinational therapeutics to overcome resistance. Ultimately, this work will be translated to benefit most of the patients with ER+ breast cancers.

Anthony Letai, M.D., Ph.D. & Joan Montero, Ph.D.

Funded in Collaboration with Stand Up To Cancer (SU2C)

Every cancer is unique pointing to the need for personalized medicine. In oncology, a fundamental challenge is to assign the right treatment to every patient due to cancers’ biological complexity and the lack of effective predictive biomarkers. At the Letai lab we developed a functional predictive assay called Dynamic BH3 Profiling to rapidly test different treatments prior to giving them to the patient. It has already been successfully proved as an excellent predictor in different types of cancer, including melanoma. We aim to combine sophisticated genomic analyses with this novel test to improve melanoma treatment, improving patients’ clinical outcome, clinical trials and drug development.

Salvatore Bertolone, M.D.

Funded by The Louisville Friends of V

Peter S. Turk, M.D.

Funded by Papa John’s International, Inc.

Michael Zinner, M.D.

Funded by Hooters of America, LLC

Baptist Health South Florida is developing Miami Cancer Institute into a destination cancer center known for its leading clinical care, exceptional patient experience, advanced clinical research and state-of-the-art technology – including the first proton therapy center in South Florida, Latin America and the Caribbean. To accelerate its mission of hope, caring and innovation, Miami Cancer Institute has announced plans to join the Memorial Sloan Kettering Cancer Alliance, a dynamic partnership that will ultimately enable cancer patients to access potential breakthrough therapies right here in South Florida.

Tian Zhang, M.D.

Funded by friends of TK and Virginia Wetherell

Metastatic castration resistant prostate cancer (mCRPC) – prostate cancer which is resistant to androgen deprivation therapy – can be often aggressive and lethal. The androgen receptor (AR) has an important role in the disease course of prostate cancer, since both enzalutamide and abiraterone acetate improve overall survival by exerting effects on the AR pathway. Our preclinical data shows that AR can increase proteins that are needed maintaining copper balance, such as the copper transporter protein, which we found in prostate cancer samples. To take advantage of the copper biology in prostate cancer, we performed a “conditional lethal” screen for drugs that exert their cancer-killing effects based on the presence of copper. This screen identified disulfiram “Antabuse”, as a potential drug for prostate cancer. Antabuse has been tested before in prostate cancer but never in the presence of copper. Mouse models of prostate cancer have shown that those cancer masses can shrink when Antabuse is given along with copper. Therefore, we propose to study the combination of Antabuse and intravenous copper, to find the safety profile for this combination of drugs. In addition, we will study the copper uptake of these patients’ prostate cancers using a radiolabeled copper PET scan. These studies will allow us to see whether the baseline copper uptake of a patient’s prostate cancer is linked to their response on the combination of Antabuse and intravenous copper.

Kenneth Westover, M.D., Ph.D.

V Scholar Plus Award- extended funding for exceptional V Scholars

Cancer is an abnormal state wherein cells become uncontrolled in their ability to divide, grow and cross tissue borders. These cellular processes are governed by an array of signaling proteins including KRAS. Mutations in the KRAS protein result in uncontrolled signaling leading to cancer. KRAS mutations are some of the most common causes of many types of cancer. However, researchers have struggled to discover ways of treating tumors driven by mutant KRAS. The goal of this project is to develop new drugs that directly target mutant KRAS proteins. We will focus on two mutations. One is common in lung cancer, KRAS G12C. The other is common in gastrointestinal cancers, KRAS G13D.

Michael Weber, Ph.D.

Funded by Virginia Vine 2016

“Precision medicine” aims to develop better treatments by understanding the molecular causes of disease. This is essential in cancer because each type (breast, brain, or blood cancer, for example) represents dozens of different kinds of cancer at the molecular level. And each of these different molecular sub-types requires different treatments.

Based on research of the past twenty years, we understand a great deal about what drives cancers. Many drugs have been devised that specifically target these causes – molecular “smart bombs.” However, the cancer cells rapidly adapt and find escape routes. Drugs that seem to work ultimately fail. We get many hopeful responses but few cures.

Our research seeks to identify and block these escape routes. We look at the molecular changes inside cancer cells after drugs are applied, and we then use other drugs to “slam the door” so the cancer cannot escape treatment. Our approach is already proving successful: We are testing one of these combinations in people to treat Mantle Cell Lymphoma. We propose to look at similar cancers that might benefit from this approach. We also want to better understand ways that cancer cells might escape from our combination treatments. Our goal is to improve responses to therapy and turn temporary responses into real cures.

Eliezer Van Allen, M.D.

Funded by the Stewart J. Rahr Foundation PCF Challenge Award:

co-funded by The Prostate Cancer Foundation and

the 2016 V Foundation Wine Celebration Fund a Need

Nearly all patients with metastatic castration resistant prostate cancer (mCRPC) develop resistance to androgen targeting agents and ultimately succumb to their disease. Recent discoveries by our group and others have demonstrated that a significant proportion of these patients harbor somatic or germline genomic defects in DNA repair defects, and targeting this genomically defined subset with therapies affecting this pathway may impact patient care. The goal of this project is to definitively characterize the genomic and functional landscape of DNA repair defects in mCRPC, clinically test the hypothesis that tumors harboring DNA repair defects preferentially benefit from immune checkpoint blockade, and explore innovative strategies to augment the efficacy of these agents through genomic and preclinical approaches. The project described herein is the first to comprehensively bridge the DNA repair and immuno-oncology fields to directly impact patients with advanced prostate cancer. We propose an integrated strategy that leverages advances in clinical genomics, trial design, and preclinical modeling methodology pioneered by our team. Furthermore, our proposal will be the first to specifically enable immune checkpoint blockade treatment strategies for mCRPC. In summary, this project will catalyze our understanding of how DNA repair defects impact advanced prostate cancer, and how deep knowledge about these events may enable clinical development of a transformative new class of immunotherapies that are greatly needed for advanced prostate cancer patients.

Hatem Soliman, M.D.

Funded by Hooters of America, LLC

This project attempts to use advanced analytical software (IBM’s Watson) to provide a comprehensive picture of our metastatic breast cancer patient population over a 5 year period at the Moffitt Cancer Center. The projects aims are to capture this dataset over the course of a year and enter in many different data points about the patients. These data points describe what this population of patients looks like from the perspective of an oncologist determining how many of them are eligible for any given trial that they have open. With this information we can use Watson to generate a detailed report to help us understand what types of patients we see, how those groups have changed over time, and most importantly what trials can we seek out to best match up with the patients we see at our center. The goal is to use data analysis to help us plan what mix of different trials we need to open in the future to best serve our patients’ needs.