Going to Extremes: Learning from Exceptional Responders to Improve Outcomes for Women with High-Grade Serous Ovarian Cancer
Abstract
As ovarian cancer researchers, we have long believed that, if we understood the basis of long-term survival in ovarian cancer patients, this could be of benefit for women who are not so fortunate. There is an important need to continue to develop new treatments for women diagnosed with this disease, especially for those women diagnosed with a type of ovarian cancer known as high-grade serous (HGSOC), which makes up ~70% of the 22,000 ovarian cancer diagnoses in America each year. On average, almost 65% of women diagnosed with ovarian cancer will die within 5 years. Some women, despite having been diagnosed with a late stage cancer that would typically be associated with a very poor outcome, have a surprising and exceptionally good response to chemotherapy. This is uncommon; only about 10% of women diagnosed with HGSOC survive for more than 10 years after their diagnosis. We call these patients exceptional responders, and our laboratory has been among one of the leading groups internationally studying causes of exceptional survival in ovarian cancer patients. As part of a large international collaboration, called the Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG), we have been working since 2012 to pool resources with other researchers worldwide to identify and examine long-term survivors of ovarian cancer (10+ years). We compare their tumors, treatment, and lifestyles with patients who have not been so lucky to understand underlying causes of extremely good treatment response. Our goal is to understand factors that contribute to long-term survival, so we can enable the development of new treatment options that could help mimic or induce a similarly exceptional response in other patients to improve patient care and overall outcomes. This approach has been successful in other tumor types, including for example, prostate cancer, where the development of anti-hormonal therapy as a standard of care occurred after noticing an exceptional response to such treatment in a patient with metastatic disease. Using data from exceptional responders to try to understand different determinants of survival is considered an important research avenue for those cancer types where survival is generally very poor. To date, as part of MOCOG, we have identified that there are a variety of reasons an HGSOC patient responds exceptionally well to treatment. These include lifestyle, such as menopausal hormone therapy use, the type of immune response their body mounts against their tumor, or the underlying genetic make-up of the women and their cancer, including a specific combination of faulty genes that makes the cancer cells more vulnerable to chemotherapy. In particular, we have already identified some exciting new avenues for further investigation, including a new cell signaling pathway that has the potential to become a key target for new drugs. This pathway is currently the focus of ongoing work in our laboratory. Through a global collaborative effort, we have identified a powerful cohort of exceptional responders and are well advanced in characterizing them. This application provides a uniquely important opportunity to leverage our current work in MOCOG. In particular, we will focus on generating information on the types and patterns of proteins present in tumor and normal cells of women whose tumors have had an exceptionally good response to treatment, comparing those with unusually short survival. We will incorporate this new data with our existing genetic, immune, and lifestyle information in a worldwide first to provide as complete as possible snapshot of these cancers. Because proteins are the targets of drug therapy, we see the inclusion of proteomic data as a vital opportunity to bring our findings closer to the clinic. We are driven by a desire to learn from these remarkable cancer survivors, who have achieved an outcome that has been the goal of ovarian cancer researchers for decades. We have the firs
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110401
Entities
People
- David Bowtell
Organizations
- United States Army
- University of Melbourne