Abstract POSTER-TECH-1121: Rapid identification and targeting of chemotherapy-resistant tumor stem cell clones in ovarian cancer
Authors: Gang Ning, Yusuke Yamamoto, Ting Zhang, Xia Wang, Lane Wilson, Suzy Torti, Molly Brewer, Christopher Crum, Frank McKeon, Wa Xian
Journal: Clinical Cancer Research (2015)

Abstract Even though ovarian cancer is typically detected very late, advances in surgery and chemotherapy have resulted in the remarkable response in most patients such that cancer is essentially undetectable at six months. However, a frustratingly large number of these patients will see a return or “recurrence” of this disease over the following year against which chemotherapy is less effective. There is now increasing evidence that this recurrent disease is the result of a very small number of cancer cells in the original cancer that are somehow “different”. These differences allow these cancer cells to avoid death from the same chemotherapy drugs that kill the other tumor cells. As a result, these so-called “resistant” cells continue to grow in number that can appear as cancer 1-3 years later in the same patient. Thus oncologists know full-well how to kill 99.9% of ovarian cancer cells, and their most pressing problem in ovarian cancer today is understanding how to kill this very small number of resistant cells. To meet this challenge we have very recently developed an exciting and perhaps revolutionary technology that may permit us to identify these rare, resistant tumor cells very soon after the patient is diagnosed with ovarian cancer. In particular, we can grow these rare resistant cells as individual clones in a testtube so that we can employ very powerful techniques to determine at a molecular level how they are different and thereby identify drugs that specifically kill them before they have a chance to multiply and participate in the recurrence of ovarian cancer. Moreover, this information will be applied to develop a method of rapidly staining tissue sections of tumor to determine the number and type of resistant cells in the tumor before therapy is begun. Using this method, we hope to determine what changes in the resistant cells that allow them to circumvent chemotherapy, and identify drugs that specifically target these changes. We anticipate that given the frequency with which resistance appears in high-grade ovarian cancer patients, our strategy of rapidly identifying and understanding resistant cells in these patients will be relevant to all of these patients. Our long-term goal is to provide a rapid means of predicting resistance in a given patient prior to the onset of therapy and more effectively target resistant cells at the onset of treatment. The ultimate aim is to more effectively prevent the clinical relapse and provide a more lasting benefit and ultimate cure to the woman with ovarian cancer. Citation Format: Gang Ning, Yusuke Yamamoto, Ting Zhang, Xia Wang, Lane Wilson, Suzy Torti, Molly Brewer, Christopher Crum, Frank McKeon, Wa Xian. Rapid identification and targeting of chemotherapy-resistant tumor stem cell clones in ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1121.