Despite progress in the understanding of tumor biology, clinical trials designed using specialized new therapies against specific biologic and genetic changes in patient’s tumors commonly fail. This is most likely, because current methods are limited by identifying those specific changes in the tumor using thousands of cells from tumor biopsies, which mask the changes in the small number of cancer cells that determine the patient’s outcome. In order to overcome this limitation these specific changes might need to be analyzed on a single cell level, given that tumors start and grow from a single cell. Even though ovarian cancer is subdivided into 5 distinct subtypes and more recently further into 4 molecular subtypes, the current treatment approach uses a one size fits all approach. Over half of women treated with the standard chemotherapy for ovarian cancer in addition to radical surgery, relapse within three years of treatment. Once relapsed, the majority of women die within five years of diagnosis. One hypothesis is that there are resistant cancer cells already present in the tumor at the time of initial treatment. While most of the cancer cells die with treatment, these resistant cells storm back and create the new resistant cancer that ultimately does not respond to treatment. Our study aims to find these few resistant cancer cells in the primary tumor and identify specific changes in these cells that could be treated by new and existing therapies. We will then analyze single tumor cells from the same tumors after they become resistant to standard chemotherapy, in mice in order to simulate, what happens to patients that are treated for ovarian cancer and have recurrence of their disease. We are able to conduct this work only now because new technology allows us to study complex changes in single cells taken from a woman’s ovarian cancer. This study is significant because it will define the different cell types present in a typical ovarian cancer, and identify the key cells leading to relapse and death. Once we identify these key cells, existing or newly developed specific therapies against the specific changes in these cells can be tested. If successful this unique approach can be used for other tumors or disease processes for true patient specific medical care.
This grant was made possible by a generous donation from Ovarian Cancer Alliance of Greater Cincinnati in honor of Sue Heitbrink.
Boris J.N. Winterhoff, MD, MS, is an assistant professor in the Division of Gynecologic Oncology at the University of Minnesota. Dr. Winterhoff, a native of Germany, completed his fellowship in Gynecologic Oncology at the Mayo Clinic. Prior to his fellowship, he did his OB/Gyn residency training and a translational research fellowship in cancer genomics at the Mayo Clinic in collaboration with UCLA. Dr. Winterhoff obtained his medical degree and a doctoral degree in molecular oncology from the Christian Albrecht’s University in Kiel, Germany.
Dr. Winterhoff has a strong background and interest in clinical translation of cancer genomics and precision medicine and its application in ovarian cancer through work in various national and international collaborations