Stopping Cancer Early – The Best Possible Investment

Biomarkers

Biomarkers (short for biological markers) are like biological ‘fingerprints’ that show the presence or progress of a disease. They will help us identify individuals who are likely to have cancer, and are a key area of our early cancer detection focus. As just one example, we are looking at blood-based biomarkers to help us predict a risk profile for lung cancer. In the area of pancreatic cancer, Canary teams are working to develop more accurate blood-based or saliva-based biomarkers.

Richard Kimura, Director of Cell Molecular Biology

Richard Kimura, Director of Cell Molecular Biology

Breast Cancer Biomarkers—Establishing Tissue Bank

Investigators at the Canary Center at Stanford are collaborating with researchers and clinicians at the Stanford Cancer Institute on a project to identify gene expression and protein changes in patient specimens as breast cancer develops, and to determine whether those changes correlate with specific imaging findings.

The team is establishing a Stanford University tissue bank of matched tumor and normal breast biopsy samples, mammography, ultrasound, magnetic resonance imaging studies, and blood samples.

The team will integrate the data and identify correlations between plasma protein and tumor gene expression profiles, pathology, and radiographic imaging studies. The dataset will represent the most comprehensive analysis of its kind to date. Potential biomarkers that signal the development of the tumor would form the basis for early detection blood tests to complement imaging.

Additional work aims to identify biomarkers that distinguish women with cancer from those with benign conditions (such as a cyst). These biomarkers would potentially reduce the number of unnecessary invasive follow-up tests and enhance the interpretation of mammographic images for early detection of breast cancer.

Lung Cancer Biomarkers—Launching Trial With 10,000

Partner stakeholders and collaborating institutions, including Canary Foundation and MD Anderson Cancer Center in Houston, Texas, are launching a clinical trial in which blood biomarker data will be incorporated into the CT screening process for lung cancer. The trial will enroll at least 10,000 individuals to be followed for three to five years at a minimum of 10 participating sites in the U.S.

At each visit, participants receive a CT scan, a questionnaire that includes detailed smoking history, and a blood draw. All participating sites will incorporate the same sets of Standard Operating Procedures for protocol design, specimen collection, processing, storage, and shipping.

Biomarkers will be tested for their ability to detect lung cancer and to discriminate cancer versus benign conditions in suspicious CT findings. Biomarkers will also be tested for their ability to predict a risk profile for lung cancer. Top biomarkers include those discovered and validated through the Canary Lung Team’s previous research on blood and tissues from lung cancers that developed in individuals who never smoked. The team is also evaluating all biomarkers that show promise from studies worldwide so that the most promising biomarkers can qualify for validation using samples from this prospective screening trial.

Ovarian Cancer Novel Markers Trial (NMT)—With Two Biomarkers, CA-125 and HE4

The Novel Markers Trial (NMT) was launched in 2009 by the Pacific Ovarian Cancer Research Consortium (POCRC), a collaborative team of scientists led by Canary team member Dr. Nicole Urban who was awarded a five-year SPORE grant by the National Cancer Institute.

Previous clinical trials of ovarian cancer screening programs mostly involved a single biomarker (CA-125) as a blood test. The NMT incorporates a second blood-based biomarker (HE4) into the screening protocols for clinical decision-making. Furthermore, the trial uses a new computational algorithm to determine whether the biomarker signals the presence of cancer. The study is determining the predictive value for malignant ovarian cancer of a screening program that includes the two blood biomarkers, the new algorithm to decipher a cancer signature from blood biomarkers, and ultrasound as an imaging modality.

The five-year study has enrolled its goal of 1,200 women, divided into three risk groups depending on the mutation status of certain cancer risk genes, family history of ovarian cancer, and other factors that may influence a woman’s risk of ovarian cancer. The study has determined that HE4 is useful as a confirmatory screen when rising CA-125 is used alone as a primary screen. The screening protocol was found to be feasible and acceptable to women and physicians and did not result in excessive imaging, surgical consults or surgeries. Thousands of well-characterized samples, including blood and tissue specimens, are now stored in a central repository for use in future studies. The NMT is under consideration to be made available nationally through an NCI-funded cancer research cooperative group.

For more detailed information about this screening trial, please visit the POCRC website.

Pancreatic Cancer Biomarkers—and Pursuing Multiple Reaction Monitoring

The blood biomarker CA-19-9 is currently the only clinically used blood test for pancreatic cancer, but it lacks the sensitivity and specificity needed to detect early-stage pancreatic cancer. The Canary team is working to develop more accurate blood-based or saliva-based biomarkers.

The team is pursuing Multiple Reaction Monitoring (MRM), in which proteins of interest are directly measured in the plasma, without the need for antibodies. This project is designed to alleviate the bottleneck of antibody development in the efforts to bring lab discoveries to the clinic. In addition to protein biomarkers in the blood, the team is also pursuing alternative biomarkers such as cancer-specific microRNAs in the saliva of patients with pancreatic diseases.

Where Canary Science is Happening

  • Canary Foundation in Palo Alto, California
  • MD Anderson Cancer Center in Houston, Texas

Canary Funded Biomarker Publications

Brooks, J.D. Translational genomics: The challenge of developing cancer biomarkers. Genome Res. (2012)

Hanash, S.M. Why have protein biomarkers not reached the clinic? Genome Med. (2011)

Borugian, M.J., et al. The Canadian Partnership for Tomorrow Project: building a pan-Canadian research platform for disease prevention. CMAJ (2010)

May, D., et al. A software platform for rapidly creating computational tools for mass spectrometry-based proteomics. J Proteome. Res. (2009)

Lutz, A.M., et al. Cancer screening: A mathematical model relating secreted blood biomarker levels to tumor sizes. PLoS Medicine (2008)

Scholler, N., et al. Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery. J. Transl. Med. (2008)

Martin, D.B., et al. MRMer: An interactive open-source and cross-platform system for data extraction and visualization of multiple reaction monitoring experiments. Mol. Cell. Proteomics (2008)