Stopping Cancer Early – The Best Possible Investment

Canary Foundation Science Update Summer 2015

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Canary Foundation Science Update Summer 2015

Canary’s mission is to demonstrate cost-effective, safe, accurate and minimally invasive tests to detect cancer early, ideally before symptoms appear and then to pinpoint its location through molecular imaging. With the help of our community, we invest in promising yet underfunded studies, guide in creating traction to attract philanthropic investment, highly competitive government funding and support from industry partners, and guide studies to clinical trials with patients. We create and foster collaborations between best-in-field researchers and seek to stimulate research in cancer early detection that is still overlooked and underfunded nationally, yet holds the key to saving lives and raising the quality of life for those diagnosed with cancer.

Improving on existing screening methods can be made available in the near-term to high-risk individuals. The goal is that as these new tests are further developed they will be used to screen larger populations. Improved tests for cancer early detection will guide treatment choices and reduce the number of unnecessary life-changing surgeries and even biopsies.

In this our 10th year we have many programs that have come to maturity that highlight our progress in numerous areas. Dr. Leland Hartwell, who received a Nobel Prize in Physiology or Medicine for advancing cancer research, recently shared at an event, “Canary Foundation is helping to make cancer early detection a national priority.” He said to Canary Foundation’s founder, Don Listwin, “Thank you for your service on the National Cancer Institute advisory board, for enabling many young scientists to test their best ideas and for giving us hope that we are in reach of the goal.”

Please accept this document as a brief update on many of our programs.

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Prostate Cancer Program Collaborating with Industry Partner OPKO: Exploring A Blood Test To Detect Aggressive Prostate Cancer

OPKO, a multinational pharmaceutical & diagnostics company, is an industry partner developed by the Prostate Active Surveillance Study (PASS). PASS is a clinical study of men choosing active surveillance for prostate cancer that helps the men enrolled to avoid unnecessary surgeries while testing blood samples to discover biomarkers for the most aggressive, deadly prostate cancers. OPKO and Canary are evaluating a panel of four blood protein biomarkers (kallikreins) for the prediction of high-grade, aggressive prostate cancer in men with low-grade prostate cancer in PASS. The goal is to see whether the 4K Score – a blood test – can signal the presence/absence of high–grade cancer that would normally be found (or not found) upon biopsy. This information could serve as a surrogate for biopsy and therefore reduce the number of unnecessary biopsies in prostate cancer management. Last year, PASS was awarded a highly competitive Department of Defense grant to increase its collaborations with industry partners.

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Breast Cancer Program: Exploring the Utility of Interstitial Fluid To Improve Breast Cancer Screening.

Mammography for breast cancer imaging is currently the best diagnostic tool that we have. However, many cancers are missed, while other masses lead to unnecessary biopsies and surgeries, and lack of information about whether the tumor is benign or cancerous, and whether a cancer is fast or slow growing, results in overtreatment. Canary Foundation’s Breast Cancer Program, anchored at the Canary Center at Stanford, is about to begin a new study that competed for and won a grant from the Department of Defense to explore the use of biomarkers in interstitial fluid (a fluid that bathes the cells in the breast) collected using a patch and causing no more pain than a mosquito bite. Levels of candidate and novel biomarkers will be measured using state-of-the art methods on interstitial fluid collected from women at the time of screening in the breast imaging clinic. The aim of the study is to improve breast cancer screening by more accurately diagnosing breast cancer and determining what extent of treatment is actually needed. This is a pre-clinical trial study with the goal of moving into clinical trial.

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Lung Cancer Program: Canary Center At Stanford Will Serve As Satellite Clinic To Broad Scale MD Anderson Clinical Trial To Improve CT Screening By Adding A Blood Test.

Canary Foundation and MD Anderson Cancer Center in Houston, Texas, together with partner stakeholders and institutions, are launching a collaborative study to build upon our previous research and to improve upon the success of the National Lung Screening Trial (NLST), which showed the benefit of computed tomography (CT) screening for lung cancer. CT screening reduces lung cancer mortality, but the technique has a high false positive rate. In addition to saving lives through low-dose CT, the goal of this study is to test the contribution of biomarkers to CT screening. Biomarkers have the potential to aid the interpretation of CT scans to reduce the false positive rate. Biomarkers may also identify individuals at risk for lung cancer who could benefit from screening. The team is launching a clinical trial in which blood biomarker data are incorporated into the CT screening process for lung cancer. The trial will enroll at least 10,000 individuals to be followed for 3 years at a minimum of 10 participating sites in the U.S. The Canary Center at Stanford will be one of the participating sites.

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Prostate and Ovarian Cancer Novel Imaging Using Ultrasound at the Canary Center at Stanford.

Innovative imaging modalities are now the subject of clinical trials using enhanced ultrasound. The first is using microbubbles, small gas-filled spheres that can be safely injected into a vein and circulate throughout the body. These microbubbles can be targeted, or coated with agents that bind to specific biomarkers, in order to produce a signal from cancer cells or their blood vessels. An initial study in Rome showed great results in prostate and ovarian cancers. Targeted microbubbles received FDA approval and are now being tested in larger trials at Stanford.

Another enhancement of ultrasound uses photoacoustics (PAI), light in and sound out, that can get through to difficult areas in the body. Over the past 5 years the Gambhir Lab has developed a photoacoustic instrument to improve the diagnostic accuracy of ultrasound in breast, ovarian, prostate, and thyroid cancer screening. The existing handheld PAI instrument was then adapted to include an ultrasound mode and has dimensions in accordance with the standard dimensions of clinical ultrasound instruments. Currently, this new device is being tested in a first clinical trial at Stanford in patients suspected for prostate cancer. Clinical trials for ovarian, thyroid, and breast cancer are to follow soon. Watch for more on these important trials. The prostate imaging will coordinate with another mature clinical trial, the Prostate Active Surveillance Study that is helping men avoid unnecessary surgery while collecting samples to find biomarkers for aggressive prostate cancers. Stanford serves as a site for this trial.

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Effectiveness for Screening for Ovarian Cancer

Our Ovarian Cancer Team has been engaged in a study called the Novel Markers Trial since 2009 at the Fred Hutchinson Cancer Research Center. This trial is designed to investigate whether adding a new biomarker (HE4) to the current screening regime (CA-125 blood test plus conventional ultrasound) will improve ovarian cancer diagnostics. The Novel Markers Trial has already shown to reduce the number of unnecessary surgeries by increasing the accuracy of testing for ovarian cancer. Since 2009, 1,200 women have been screened regularly using this process, allowing for the collection of important tissue, blood and data. The trial is exploring markers that will specifically identify women who should be screened.

One way of examining effectiveness is to compare results of one study with another. The Prostate, Lung, Colorectal, and Ovarian Screening Trial (PLCO), a large-scale study conducted by the National Cancer Institute to determine the effects of screening on cancer-related mortality and secondary endpoints in men and women aged 55 to 74, sets a benchmark for screening. The PLCO trial ended in 2008 and they continue to analyze data. In that trial there were 20 surgeries performed for every 1 ovarian cancer detected. In the Canary and NCI-supported Novel Markers Trial, there were 3 surgeries for every 1 cancer detected showing that ovarian cancer screening is improved when a second biomarker is added. We are awaiting the results of a current large screening trial just completed in the United Kingdom, targeted to be available in December 2015, to make further comparisons.

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Canary Center at Stanford for Cancer Early Detection

Since 2007, Canary Foundation has been involved in a unique partnership with Stanford University. This resulted in the creation of the Canary Center at Stanford for Cancer Early Detection. The Center is led by Dr. Sanjiv “Sam” Gambhir, chair of radiology at Stanford who also serves as director of the Canary Center at Stanford. Canary Foundation continues to support innovative studies and to help develop the Canary Center by raising funds for faculty recruitment and lab enhancements.

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Flipping The Problem Around – Forcing Tumors To Produce A Measurable Known Biomarker Instead Of Looking For Elusive Cancer Biomarkers – Canary Center Study.

Researchers have been looking for cancer-specific biomarkers, generally proteins shed by a cancer tumor, to use in finding cancer early. These biomarkers have been difficult to find. One challenge is that tumors may produce such small amounts of biomarkers in the blood that they are not measurable above the amounts naturally made in healthy tissues. Earlier this year, Dr. Gambhir’s lab announced a leap forward in research by creating a strategy that, in animal studies, causes tumors, but not healthy cells, to shed into the blood measurable amounts of a protein biomarker called secreted embryonic alkaline phosphatase (SEAP).

Here’s how it works. This new process uses DNA minicircles, tiny rings of DNA, which enter a cancer cell and turn on the cell’s machinery to make RNA. The RNA then produces SEAP. While the minicircles infiltrate all cells in the body, healthy cells do not make SEAP because researchers added a “switch,” called a promotor, that only activates in cancer cells. After minicircles are introduced to the body, the promoter activates within about 48 hours to create SEAP. The minicircles degrade and in about two weeks are no longer in the body. Canary Foundation continues to support innovative technologies and elegant solutions to long-standing problems.

“[We] hijacked concepts, if you will, and wanted to make cancer cells use something they don’t normally, with no immune response, and safely. That’s why minicircles making SEAP is at the heart of this,” Gambhir said. Other proteins beyond SEAP may become part of the process.

This study, which won National Institutes of Health funding, is seen as potentially having high-impact on large populations in a short time-span of 5-10 years, and will be positioned to move into clinical studies.

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Canary Center at Stanford: Attracting Top Researchers

To implement new discoveries in the clinic, work at the Canary Center is committed to developing novel micro- and nanoscale bioengineering and biomedical microfluidic technology platforms to enable clinical diagnostics and point of care tests. To achieve this goal, Dr. Utkan Demirci from Harvard Medical School and Dr. Tom Soh from UCSB have recently been recruited to lead special technology development efforts.

Dr. Utkan Demirci (Harvard): A Microfluidic Technology Platform

Dr. Demirci’s previous efforts have yielded a point of care microchip technology to detect ovarian cancer biomarkers (e.g., HE4) using a 10-minute microchip assay and a cell phone as the detector. Dr. Demirci will continue to innovate around point of care diagnostics, microfluidics assays and the development of technology platforms at the convergence of engineering, biology and materials science. Dr. Demirci brought his 15-person lab from Harvard to the Canary Center at Stanford.

Dr. Tom Soh (UC Santa Barbara): Biosensors For Point Of Care Diagnostic Platforms

Dr. Tom Soh focuses on the directed evolution of organic materials that do not exist in nature, but can perform extremely useful functions for many biotechnical applications including molecular diagnostics. His work also focuses on integrated biosensors. The goal is to create portable, rapid, and sensitive diagnostic platforms to be used at point-of-care. Dr. Soh is currently moving his lab to the Canary Center at Stanford.

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Canary Foundation Continues to Seed Promising Studies

Clinical trials for breast cancer detection with a wearable sensor from Cyrcadia Health

One of the challenges with mammography is its lower rate of cancer detection in women with dense breast tissue. At the same time, mammography has a high rate of false positives, resulting in unnecessary biopsies. Mammography also involves radiation exposure and potentially uncomfortable breast compression. To address some of these issues, Cyrcadia Health developed a flexible, wearable set of sensors that is placed inside a bra for 12 hours. The device is designed to measure circadian rhythm-based temperature variations that occur at the cellular level. Abnormalities could signal the early stages of breast cancer.

The company is testing this technology’s ability to distinguish cancer in patients enrolled at El Camino Hospital in Mountain View. Women with a suspicious finding upon mammogram will be offered the wearable sensor prior to biopsy. The ability of the sensor to risk stratify women prior to biopsy will be determined. If trials are successful, the sensor could be used to help women avoid unnecessary biopsies during breast cancer screening. Trials have begun this summer and aim to enroll approximately 175 patients at two sites in the U.S., including those at El Camino. A future application of this product is to allow personal monitoring of breast health, particularly in women with dense breast tissues, as a means to screen for early signs of breast cancer in the high-risk population. Canary has provided support for this study.

Colon Cancer Research

Canary Foundation and the Canary Center at Stanford will lay the foundation for a program in early detection tests for improving colon cancer diagnostics. The Canary Center at Stanford will begin discovery research by collaborating with Vanderbilt University, where they have collected thousands of colon cancer samples, providing a rich repository of material that is difficult to gather. This study will utilize the relatively new field of proteogenomics that employs mass spectrometry, a chemical process designed to measure proteins in cancer research, in determining the role genes play in cancer. Additionally, innovative imaging projects for colon cancer are underway at the Canary Center.

Pancreatic Cancer

The Canary Pancreatic Cancer Team is working to develop blood-based or saliva-based biomarkers, in combination with molecular imaging, to detect pancreatic cancer early. 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.

The Canary Team is also developing new imaging agents to discriminate pancreatic cancer compared to benign diseases, as well as small early-stage pancreatic tumors. The team has demonstrated the ability to detect small pancreatic cancers, less than 1 millimeter in size, using ultrasound with targeted microbubble technology in mouse models of pancreatic cancer. The team has discovered a new candidate biomarker for pancreatic cancer imaging, Thymocyte Differentiation Antigen 1 (Thy1). Thy1 is expressed in vascular endothelial cells early in pancreatic cancer development. Ultrasound imaging with Thy1-targeted microbubbles in mouse models of pancreatic cancer shows promise, as the imaging agent visualizes pancreatic cancer and not benign disease. Thy1 is also being developed for other imaging modalities, including photoacoustic imaging.

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Canary Science Symposium 2015: Continuing to Foster Innovation and Collaboration

Canary hosts the Canary Science Symposium with 180 researchers from across the nation and the world. The meeting serves as a venue to bring everyone together who is working on, passionate about, and/or invested in cancer early detection in one place to discuss their work, discover connections and pursue collaborations.

Highlights from this year’s symposium included learning about the successful launch of the Cologuard colon cancer diagnostic test from one of its inventors (David Ahlquist, Mayo Clinic), seeing data from the first clinical trials in the United States featuring targeted microbubbles (Jürgen Willmann, Stanford), and seeing data on circulating tumor cells being characterized in patients being screened for lung cancer right here at Stanford (Peter Kuhn, University of Southern California).

As 2015 marked the year of the 10th Symposium, our founder, Don Listwin, reflected on the exciting progress we have made over the past decade, with a trend of moving our research into the clinic and into the marketplace. To commemorate the 10th Symposium, Canary held a poster competition, with high caliber entries from over 45 presenters. The winners were announced as: Jesse McKenney, Cleveland Clinic, who examined 1275 patients from the Canary Prostate tissue microarray study to uncover new patterns to predict the outcome of their cancer; Sharon Hori, Stanford University, who modeled the release of biomarkers into the blood as tumors developed from early stages; and Nathalie Scholler, SRI International, who showed elegant research targeting the immune system’s B cells to fight ovarian tumors.

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Questions? Please contact Therese Quinlan at