Font: Small | Medium | Large
Ovarian Cancer Program

Motivation

Early detection of ovarian cancer promises to save the lives of thousands of women each year.

Over 230,000 women are diagnosed with ovarian cancer each year worldwide, including approximately 22,000 women in the United States.1 Unfortunately, the majority of these women ultimately die from this disease: ovarian cancer is responsible for an estimated 140,000 deaths per year worldwide, including over 15,000 deaths per year in the United States.1 The average lifetime risk of ovarian cancer for women in the US is approximately 1 in 70.1,2

Ovarian cancer is known as the 'silent killer' because most women are not diagnosed until the cancer has already spread, and chances of survival are poor (Figure 2). In contrast, if it is caught early enough, ovarian cancer can often be cured with current treatments (Figure 3). Thus, there exists a major opportunity to save lives through early detection of ovarian cancer. Ultimately, a major reduction in mortality due to ovarian cancer will require screening of the general population, as the vast majority of cases of ovarian cancer arise in women without a family history of cancer.3,4

Figure 2: Stage of Diagnosis Figure 3: Survival by Stage of Diagnosis

Research

Canary Foundation applies a collaborative approach towards biomarker discovery, validation, and translation into early detection tests.

The goal of our ovarian research program is to develop a strategy to accurately identify ovarian cancers that would otherwise be lethal at a stage when they are readily curable. Our vision is of a two-stage screening strategy, consisting of a simple blood test followed by a molecular imaging test. Development of blood and imaging tests follow a similar roadmap, both including biomarker discovery followed by validation, but involve different techniques and challenges.

Blood-Based Biomarkers

The ideal blood biomarker is a protein or other biomolecule whose abundance in the blood (or other fluid) is consistently higher (or lower) in women harboring very early stage ovarian cancers relative to women without cancer. We anticipate that no single biomarker will be a 'silver bullet' but rather that a definitive diagnosis will be made based on measurements of several biomarkers at once (i.e. a 'biomarker panel').

Discovery

The first biomarker discovery project undertaken by Canary's ovarian cancer team involved in-depth molecular characterization of ovarian cancer cell lines, which serve as a renewable model of ovarian cancer. We subsequently extended this comprehensive molecular profiling approach towards ovarian cancer tumor tissues and ascites-derived tumor cells. Most recently, we added projects to discover novel protein biomarkers directly in the blood of women with pre-symptomatic ovarian cancer. We continue to augment and mine this remarkable resource of genomic, proteomic, and epigenomic profiles of a standardized set of ovarian biospecimens.

Validation

  • Assay Development - For most novel biomarker candidates, the first step in validation is development of an assay to measure this biomarker in the blood or other fluids. Only then can the biomarker be either eliminated or advanced as a candidate for our early detection panel. To address this critical bottleneck, Canary Foundation supported the development of a dedicated biomarker validation team in Victoria, Canada. This team has built a system for efficient development of assays that is being highly leveraged by all Canary cancer programs.
  • Clinical Specimens - In order to be effective, our biomarker panel must definitively signal cancer in the tiny fraction of apparently healthy women in whom ovarian cancer has begun to develop. Access to clinical specimens, particularly from women prior to disease diagnosis, and from large numbers of non-diseased controls, is a critical part of biomarker validation. We are building a consortium that will allow us to test our leading biomarkers in these precious specimens.

Imaging Biomarkers

Molecular imaging allows us to 'see' tumors based on specific, unique, molecular characteristics. Our ideal biomarker for molecular imaging is a protein (or other biomolecule) that is highly abundant on the surface of tumor cells (or associated cells) but absent from the surface of all other cells in the body. Given a specific labeled probe that binds to this biomarker, we can visualize the tumor directly inside the woman being screened. We are pursuing two different molecular imaging approaches in our ovarian molecular imaging program: 1) PET imaging of proteins found on the cell surface of ovarian tumors and 2) ultrasound imaging of proteins found on blood vessels associated with ovarian tumors using a novel microbubble-based approach.

Discovery

  • Three leading candidate PET imaging protein biomarkers were identified through a combination of molecular data on ovarian tumors and literature review.
  • We are actively engaged in discovery and prioritization of candidate protein biomarkers for ultrasound/microbubble based imaging of tumor-associated blood vessels.

Validation

  • Antibodies have been used to evaluate our leading PET imaging cell-surface targets in our standardized set of ovarian cancer cell lines.
  • Specific probes for PET-based imaging are being developed against each leading target to enable further validation in mouse models of ovarian cancer.
  • Molecular imaging probes that perform well in mouse models will move forward to testing in human subjects.

Ovarian Cancer Progression

One of the challenging aspects of building a test for early detection of ovarian cancer is that the earliest stages of ovarian cancer development are not well understood. In ovarian cancer, the early precursor lesion has not been identified, and recent molecular studies have lent support to the theory that some (or most) ovarian cancers originate in the fallopian tube rather than the ovaries. It is also unclear how rapidly the lethal ovarian cancers progress from localized and curable to metastatic and incurable. To help address these critical knowledge gaps, we supported an in-depth pathological analysis of fallopian tubes from women at high risk of ovarian cancer as well as a literature-based meta-analysis of the characteristics of very early ovarian cancers.

View Canary Funded Projects

Citations

  1. Cancer Facts & Figures 2008. American Cancer Society, Atlanta, GA, 2008.
  2. Ries LAG, Harkins D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Eisner MP, Horner MJ, Howlader N, Hayat M, Hankey BF, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER web site 2007
  3. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, Fan I, Wong B, Narod SA. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 2001 Mar;68(3):700-10. Epub 2001 Feb 15.
  4. Schildkraut JM, Thompson WD. Familial ovarian cancer: a population-based case-control study. Am J Epidemiol. 1988 Sep;128(3):456-66.