2022 Collaborative Research Development Grant Recipient — Benjamin Bitler, PhD

Benjamin Bitler, PhD

University of Colorado - Denver

A Machine Learning Approach to Chemotherapy-induced Remodeling of the Tumor

Project Summary

All patients battling ovarian cancer will undergo chemotherapy and surgery. Unfortunately, most patients will experience disease recurrence leading to secondary treatment interventions. Thus, to improve patient outcomes there is a significant need to advance the predictive power of when a tumor will recur and provide a tumor-tailored secondary treatment. The Ovarian Cancer Research Group at The University of Colorado, recently reported that the predictive signatures and secondary treatment information can be inferred from how the tumor responds to upfront chemotherapy. Using cutting-edge molecular profiling of patient-matched tumors before and after chemotherapy, the investigative team honed in on several key biological processes including transcriptional regulation (CEBP/b) and cell signaling (Wnt) that are critical for predicting disease recurrence. Moreover, using advanced computational analysis these inferences can be used to provide meaningful clinical information. The proposed research aims to expand the Ovarian Cancer Research Group’s findings and to mechanistically determine critical attributes that predict disease recurrence. The Ovarian Cancer Research Group consists of a diverse and synergistic team of clinicians, basic science researchers, computer scientists, and biostatisticians. The research group is highly capable of completing the proposed work and translating the findings into a clinical trial. The long-term vision is to be able to perform advanced molecular analysis and computer modeling on patient tumors before and after chemotherapy in a clinically meaningful timeframe so that the gynecologic oncologist would have both a reliable estimate of recurrence and a secondary treatment option tailored to the tumors.

Bio

My career goal is to put myself out of a job by eradicating ovarian cancer. As the son of two Air Force officers, I had the privilege of growing up all over the world, including Korea and Germany. These experiences provided unique perspectives and an appreciation for different cultures. Biology was my main interest in school – I was fascinated by how numerous cell types and signaling pathways performed in a spectacular orchestra to sustain "life." As I started my journey to become a medical doctor, my mom was diagnosed with breast cancer. As my mom fought her cancer, it became abundantly clear that significant and urgent improvements were needed in the fight against cancer. As a result, my career goals became more focused – to define the biological underpinnings of cancer and to expand the arsenal of anti-cancer tools. At the University of Arizona, I completed my Bachelor of Science in General Biology followed by my Doctor of Philosophy in Cancer Biology. As a graduate student, I focused on examining cancer-specific protein-protein interactions and optimizing novel therapies to target breast cancer cells. After graduate school, I moved to the Fox Chase Cancer Center in Philadelphia, PA. As a post-doctoral fellow, this was my introduction to ovarian cancer. I quickly realized a significant gap existed in scientific and clinical ovarian cancer knowledge. I also recognized that achieving this goal required a cutting-edge basic science research program integrated with a robust clinical practice. The University of Colorado stood out as an institute that met this requirement and provided a path to achieving my goal. Since joining the University of Colorado, I have worked tirelessly to build a team of clinical and research collaborators who share my passion for eradicating ovarian cancer. The Gynecologic Oncology Research Program at the University of Colorado is supported by the Divisions of Reproductive Science and Gynecologic Oncology, generous and motivated philanthropists, and competitive research grants, including the Ovarian Cancer Research Alliance (OCRA) Collaborative Research Development Grant. The Gynecologic Oncology Research Program has three main research goals: 1) To overcome therapy-resistant ovarian cancer, 2) To define the biological underpinnings of ovarian cancer, and 3) To develop strategies to prevent ovarian cancer. We actively address the research goals through several highly collaborative research projects. Since November 2016, the University of Colorado Ovarian Cancer Research Group has developed a pipeline to assess ovarian cancer tumor composition and transcriptional profiles longitudinally. The research group, funded by the OCRA Collaborative Research Development Grant, consists of cancer biologists (Drs. Bitler, Sikora, and Richer), a computer scientist (Dr. Clauset), a gynecologic oncologist (Dr. Behbakht), a pathologist (Dr. Wolsky), and an immunologist (Dr. Jordan). We appreciate that improving ovarian outcomes will require the work of multi-disciplinary teams. The OCRA award will provide pivotal funding to expand our pipeline and empirically define several factors' contribution in driving therapy response. Our vision is to use cutting-edge technology with machine learning in a clinically meaningful timeframe to predict disease recurrence and inform clinical decisions.