Stopping Cancer Early – The Best Possible Investment

The new Canary Center for Early Cancer Detection at Stanford is the first facility of its kind to bring together scientists from the fields of blood-based diagnostics with molecular imaging diagnostics. We will imagine, invent, and innovate.

Dr. Sanjiv Gambhir
Chair of Radiology, Stanford University & Canary Center at Stanford team leader

Canary Center at Stanford

At the Canary Center at Stanford, world-class scientists from different disciplines combine their strengths to build tools for early cancer detection with the ultimate goal of saving lives.

The mission of the Canary Center at Stanford is to foster research leading to the development of blood tests and molecular imaging approaches to detect and localize early cancers, because early intervention is far more effective than late stage cancer treatment. We envision a two-pronged diagnostic strategy consisting of blood-based diagnostic tests to identify individuals who are likely to have cancer, paired with molecular imaging to pinpoint and verify a specific cancer type. The Canary Center at Stanford is the first in the world to integrate research on both in vivo and in vitro diagnostics to deliver these tests, by housing state-of-the-art core facilities and collaborative research programs in molecular imaging, proteomics, chemistry, and bioinformatics. These initiatives have extensive links to the Cancer Center at Stanford, forming a direct pipeline for the translation of early cancer detection research into clinical trials and clinical practice.

Saving Lives Through Early Cancer Detection

The future could include cancer screening as simple as a urine or blood test at your annual physical or an inexpensive imaging test. Signs of cancer could be exposed before they technically become cancerous. And treatment could be so minor that you might forget you were ever treated.

Finding Early Cancer—the Needle in the Haystack

Bringing top scientists, clinicians, and engineers together, the Canary Center at Stanford is the only place exclusively committed to developing both blood and imaging tools and techniques for the early diagnosis of the world’s most aggressive cancers.

Armed with the latest technology, brightest scientists, and newest scientific advancements, finding early signs of cancer is no longer like searching for a needle in a haystack. Scientific advances in genetic sequencing, information technology, diagnostic testing, and advanced imaging techniques now allow us to see more clearly and make identifying early signs of cancer a realistic possibility.

To realize our vision, saving lives through cancer early detection, we at the Canary Center will discover and implement minimally invasive diagnostic and imaging strategies for the detection and localization of aggressive cancers at early, curable stages. This will be achieved through basic and translational research, interdisciplinary education, and the development of a model organizational infrastructure.

In the short-term, we will expand our network of interdisciplinary scientists, clinicians, biotech experts, students, and trainees. This will be achieved through various means, hiring new faculty, incorporating affiliate faculty, and expanding partnerships with scientific, clinical, industry, and community partners. We will develop robust mechanisms that foster collaboration, and these will support the development and implementation of targeted, innovative, and interdisciplinary basic and translational research that has greater breadth, depth, and success. We will also create a model scientific and organizational infrastructure to facilitate these activities.

Our Future—From Discoveries to Clinical Practice

In subsequent years, we will continue this work but will also begin building the infrastructure needed to translate discoveries into clinical practice and to create “the” international educational “hot-spot” for early cancer connections and training. All of these activities will fuel the development of minimally invasive strategies that can be used every day by clinicians around the world. As successes occur, we at the Canary Center are committed to sharing breakthroughs broadly with communities, clinicians, and scientists to ensure that impacts have multiplying effects.

World-Renowned Team

Dr. Sanjiv Sam Gambhir leads the Canary team. He is a world-renowned expert in molecular imaging and the Chair of the Radiology department and Virginia and D.K. Ludwig Professor of Cancer Research at the Stanford School of Medicine.

The Canary Center team currently consists of five faculty members and their research groups, all with different areas of expertise, selected to complement one other in finding innovative approaches to early cancer detection. And while the team continues to grow, we also have over 30 associate members that have broad reach into the university from radiology to genetics, urology, electrical engineering, health and policy, immunology, materials science, pathology and more. They are collaborating on some exciting early cancer detection techniques.

Examples include looking at tumor progression with high-throughput omics techniques and integrative statistical approaches. Or exploring isolation and molecular characterization of circulating tumor cells as a predictive biomarker. Another associate has developed an integrated sensor that can be packaged with Bluetooth or WiFi communications and easily worn by humans someday to provide real-time continuous tracking of specific cancer or stem cells. This could be particularly effective for tracking and early detection of cancer patients who are in remission.

The Canary Center encourages collaborations between research groups by awarding seed grants to innovative joint research proposals.

Learn about our associate members.

Full members include:

Dr. Sharon Pitteri is a chemistry and proteomics expert. Her group focuses on the discovery and validation of proteins that can be used as molecular indicators of risk, diagnosis, progression, and recurrence of cancer, and the identification of proteins that can be used as novel targets for molecular imaging technologies.

Dr. Parag Mallick specializes in proteomics and systems biology. His group applies systems biology to complementary computational and experimental methods to gain insight in complex biological processes such as cancer. His approach aims to answer questions about the likely behavior of the cancer, such as its aggressivity, likely outcome, response to therapy, and evolution.

Dr. Juergen Willmann is a clinical radiologist and expert in translational molecular imaging. His group focuses on the development and clinical translation of imaging biomarkers with a special focus on abdominal and pelvic cancer (liver, ovarian, pancreatic, prostate and renal cancer). They also further advance clinically available radiological imaging modalities as promising tools for early detection of cancer.

Dr. Utkan Demirci is an electrical engineer with expertise in micro- and nanoscale technologies. His group focuses on the application of these innovative technologies, such as microfluidics, to clinical problems. One of their goals is to create disposable point-of-care diagnostics to detect and monitor various types of cancer and infectious diseases.

Dr. Tom Soh is an expert in materials science and mechanical and electrical engineering. His group focuses on the development of new materials and devices to improve early detection and personalized treatment for many diseases including cancer. Real-time biosensors that measure specific biomolecules and evolved polymer materials that perform molecular recognition and shape-changes are examples of approaches that can improve molecular diagnostics and targeted therapies.

Progress and Results

Mathematical Models of Cancer Biomarker Shedding and Tumor Growth
Research from the Gambhir Lab entitled “Mathematical Model Identifies Blood Biomarker-Based Early Cancer Detection Strategies and Limitations” was featured on the cover of the journal Science Translational Medicine. Sharon Hori and Sanjiv Sam Gambhir developed a mathematical model relating blood biomarker levels to tumor growth, and computationally showed that current clinical biomarker assays are likely incapable of detecting a tumor smaller than an olive, where in some cases the tumor may have been present for at least 10 years.

The mathematical model developed here can be applied to virtually any solid cancer and associated biomarkers shed to help identify better candidate biomarkers and other strategies for early cancer detection.

Science Translational Medicine article
Nature Reviews Cancer research highlights
Clinical Chemistry article
Cancer Discovery article
Cancer Research UK website article
National Cancer Institute, Office of Physical Sciences Oncology article
Stanford School of Medicine newsletter article
ConsumerAffairs.com article
GenomeWeb website article

Detecting Cancers Through Tumor-Activatable Minicircles that Lead to a Detectable Blood Biomarker

New work from the Gambhir Lab published in PNAS uses a unique strategy to force tumor cells (if they exist) to produce a blood biomarker that would otherwise not be present.

This approach holds significant promise as a new way to tackle the early detection of cancer because it is not dependent on molecules that cancer cells naturally shed that enter the blood.

Here’s a list of related articles:

Listen to the KABC TalkRadio Interview with Dr. Drew
Listen to the Interview with Frank Ling
FoxNews article
The Scientist article
Demanjo article
Science Daily article
China.org article
Healthcare Asia article
Hindustan Times article
Hindu Business Line article
GenomeWeb article
NDTV article
Health News Latest article
ZME Science article
Medindia article
Diajiworld article
Newsly article
News24 article
Mid-Day article

 

Circulating Tumor Cells for Lung Cancer Early Detection

Lung cancer kills more people than any other cancer in this country. Although imaging and surgery are the mainstay for identifying and treating early cancers for the most common type, non-small cell lung cancer (NSCLC), recurs in 30 to 40 percent of these patients despite treatment.

Therefore, more effective tools are required to improve survival early in a lung cancer’s history. Blood biomarkers are one potential and promising approach, particularly Circulating Tumor Cells (CTCs), which detect micrometastatic disease in peripheral blood. We know that CTCs are abundant in late-stage cancers of diverse forms, and we know now that they are abundant in its early stages as well using next-generation molecular technologies based on morphologic characterization, nanofluidics, magnetic sifting, and filtration. Over the past three years, Dr. Carlssson A. Nair, with support from the Canary Foundation, has worked with a team of leading investigators to demonstrate that CTCs are a novel diagnostic tool for detecting early-stage disease using a next-generation CTC platform. He continues to carry forward those initial observations of CTCs into an ongoing and maturing observational cohort of lung cancer patients to explore the role of CTCs for surveillance and prognosis of early lung cancers over time.

Circulating tumor microemboli diagnostics for patients with non-small-cell lung cancer. Carlsson A, Nair VS, Luttgen MS, Keu KV, Horng G, Vasanawala M, Kolatkar A, Jamali M, Iagaru AH, Kuschner W, Loo BW Jr, Shrager JB, Bethel K, Hoh CK, Bazhenova L, Nieva J, Kuhn P, Gambhir SS. J Thorac Oncol. 2014 Aug;9(8):1111-9. doi: 10.1097/JTO.0000000000000235. PMID: 25157764

An observational study of circulating tumor cells and (18)F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer.
Nair VS, Keu KV, Luttgen MS, Kolatkar A, Vasanawala M, Kuschner W, Bethel K, Iagaru AH, Hoh C, Shrager JB, Loo BW Jr, Bazhenova L, Nieva J, Gambhir SS, Kuhn P. PLoS One. 2013 Jul 5;8(7):e67733. doi: 10.1371/journal.pone.0067733. Print 2013. PMID: 23861795

 

Early Detection of Pancreatic Cancer

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related death, with an average five- year survival rate of six percent.

Since less than 20 percent of patients can undergo potentially curative surgery and current therapies are not efficient, our only hope to improve survival from this disease is earlier detection.

The Translational Molecular Imaging Lab (TMIL) has shown substantial progress in developing a novel imaging approach, ultrasound molecular imaging, using contrast agents specifically designed to attach to early pancreatic cancer. We have employed two different approaches. First, we utilized the expression of the angiogenesis receptor VEGFR2 within the tumor vasculature as a molecular target for imaging pancreatic cancer with a novel clinical grade contrast microbubble. We showed that small developing tumors in the 2-7 mm size range expressed high VEGFR2 levels to allow detection with a high signal to noise ratio (1). Second, in collaboration with the University of Washington, we identified a new vascular marker of pancreatic cancer, Thy1\CD90 that is differentially expressed in pancreatic cancer but not in benign pancreatic tissue or patients with chronic pancreatitis. We developed a pre-clinical microbubble specific for this protein and were able to identify small foci of pancreatic cancers with this molecular imaging technique (2). We are currently creating a clinical-grade version of this targeted microbubble for detecting small pancreatic cancers in patients.

(1) Pysz, M. A., S. B. Machtaler, E. S. Seeley, J. J. Lee, T. A. Brentnall, J. Rosenberg, F. Tranquart and J. K. Willmann (2015). Vascular Endothelial Growth Factor Receptor Type 2–targeted Contrast-enhanced US of Pancreatic Cancer Neovasculature in a Genetically Engineered Mouse Model: Potential for Earlier Detection. Radiology 2015; 274(3): 790-799.
(2) Foygel, K*., H. Wang*, S. Machtaler*, A. M. Lutz, R. Chen, M. Pysz, A. W. Lowe, L. Tian, T. Carrigan, T. A. Brentnall and J. K. Willmann. Detection of pancreatic ductal adenocarcinoma in mice by ultrasound imaging of thymocyte differentiation antigen 1. Gastroenterology 2013; 145(4): 885-894 e883.

 

Early Detection of Pancreatic Cancer

Ultrasound molecular imaging is a highly sensitive imaging modality that plays a major role in the field of cancer imaging by contributing to earlier detection and characterization of focal lesions (1).

Using the first clinical-grade, molecularly targeted ultrasound contrast agent (BR55), targeted against human VEGFR2, has enabled us to assess tumor progression and differentiating normal from cancer tissue with high diagnostic accuracy in transgenic mouse models of breast cancer (FVB/N-Tg (MMTV-PyMT) 634Mul) that resemble tumor progression in patients (2). In this mouse model in vivo imaging signal significantly increased as the mammary gland tissue progressed from normal to hyperplasia, ductal carcinoma in situ (precursor lesions) and invasive breast cancer due to an increase in the number of tumor vessels and the magnitude of VEGFR2 expression levels per tumor vessel.

Recently, we detected and validated a novel breast cancer associated molecular marker, B7-H3 (CD276, a member of B7 family of immunomodulators) to be differentially expressed in breast cancer compared to benign lesions and normal breast tissue in a large scale IHC analysis of patient breast tissues (2). We also designed a new contrast agent targeted at B7-H3 and tested it in a breast cancer and ovarian cancer mouse model (3).

(1) Bachawal SV, Jensen KC, Lutz AM, Gambhir SS, Tranquart F, Tian L, et al. Earlier detection of breast cancer with ultrasound molecular imaging in a transgenic mouse model. Cancer Res 2013;73:1689-98.

(2) Bachawal SV, Jensen KC, Wison K, Tian L, Lutz AM, Willmann JK. Breast cancer detection by B7-H3 targeted ultrasound molecular imaging. Cancer Research 2015 (in press)

(3) Lutz AM, Bachawal SV, Drescher CW, Pysz MA, Willmann JK, Gambhir SS. Ultrasound molecular imaging in a human CD276 expression-modulated murine ovarian cancer model. Clin Cancer Res 2014;20:1313-22.

The Mallick Lab—Multi-omic Discovery

The Mallick lab, under the direction of Dr. Parag Mallick focuses on translating multi-omic discovery into precision diagnostics. This lab uses integrative, multi-omic approaches to model the processes that govern proteome dynamics and then employs those models to discover cancer biomarkers and mechanisms.

In the Mallick Lab, lab coats and goggles must be worn at all times. Clipboards are optional, but recommended.

In the Mallick Lab, lab coats and goggles must be worn at all times. Clipboards are optional, but recommended.

In particular we use tightly integrated computational and experimental, multi-omic approaches to discover the processes underlying how cells behave (or misbehave) and accordingly how cancers develop and grow. We hope that by exploring these processes, and by formalizing our knowledge in predictive mathematical models that we will be able to better identify biomarkers that can be used to detect cancers earlier and describe how they are likely to behave (e.g. aggressive vs. indolent, drug sensitive vs. responsive).
http://mallicklab.stanford.edu/index.php/research

Check Out the Latest Papers

  • ProteoWizard (Nature Biotech)
  • Cell Squishyness & Sliminess & Metastatic Potential (PNAS)
  • Physical Sciences Characterization of Metastasis (Nature Scientific Reports)
  • SWATH MS Libraries (Nature Protocols)

Pitteri Labaratory—Discovery and Validation of Proteins as Molecular Indicators of Cancer

The Pitteri laboratory, under the direction of Dr. Sharon Pitteri, is focused on the discovery and validation of proteins that can be used as molecular indicators of risk, diagnosis, progression, and recurrence of cancer.

CCS Pitteri Lab

Dr. Sharon Pettiri (right) in her lab, which is focused on the discovery and validation of proteins that can be used as molecular indicators of risk, diagnosis, progression, and recurrence of cancer.

Proteomic technologies, predominantly mass spectrometry, are used to identify proteins in the blood that are differentially regulated and/or post-translationally modified with disease state. Using human plasma samples, tumor tissue, cancer cell lines, and genetically engineered mouse models, the origins of these proteins are being investigated. A major goal of this research is to define novel molecular signatures for breast and ovarian cancers, including particular sub-types of these diseases. This laboratory is also focused on the identification of proteins with expression restricted to the surface of cancer cells that can be used as novel targets for molecular imaging technologies.

Check Out the Latest Papers

Intact MicroRNA Analysis Using High Resolution Mass Spectrometry JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY Kullolli, M., Knouf, E., Arampatzidou, M., Tewari, M., Pitteri, S. J.2014; 25 (1): 80-87

Performance evaluation of affinity ligands for depletion of abundant plasma proteins JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES Kullolli, M., Warren, J., Arampatzidou, M., Pitteri, S. J.2013; 939: 10-16

Demirci Lab

The Demirci Bio-Acoustic MEMS in Medicine Labs (BAMM) laboratory specializes in applying micro- and nanoscale technologies to problems in medicine at the interface between micro/nanoscale engineering and medicine.

We apply innovative technologies to clinical problems. Our major research theme focuses on creating new microfluidic technology platforms targeting broad applications in medicine. In this interdisciplinary space at the convergence of engineering, biology and materials science, our goal is to create novel technologies for disposable point-of-care (POC) diagnostics and monitoring of infectious diseases, cancer and controlling cellular microenvironment in nanoliter droplets for biopreservation and microscale tissue engineering applications. These applications are unified around our expertise to test the limits of cell manipulation by establishing microfluidic platforms to provide solutions to real world problems at the clinic.

Our lab creates technologies to manipulate cells in nanoliter volumes to enable solutions for real world problems in medicine including applications in infectious disease diagnostics and monitoring for global health, cancer early detection, cell encapsulation in nanoliter droplets for cryobiology, and bottom-up tissue engineering.

Dr. Demirci is involved in inventing disposable, rapid, and user-friendly develop tools to check for biomarkers in the comfort of one’s home.

Check Out the Latest Papers

Clinical Studies

EDRN Projects
The work of the Early Cancer Detection Research Network (EDRN) is to address a key unmet need in prostate cancer early detection and management: improving the screening process for this major epithelial cancer.

Project 1 entails the adaptation of our newly developed magneto-nanosensor for the multiplex analysis of blood biomarkers for prostate cancer detection and prognostication.
(Use of clinical samples from prostate cancer patients and patients with BPH.)

Project 2 entails the adaptation of our latest ultrasound technology using tumor angiogenesis-targeted microbubbles to image prostate cancer. Now in clinical trial:
“A Pilot Trial Using BR55 Ultrasound Contrast Agent in the Assessment of Prostate Cancer.“ (Juergen Willmann, Sam Gambhir, Jim Brooks)

Other Studies

Photoacoustic Imaging (PAI) of the Prostate: A Clinical Feasibility Study. (Sam Gambhir, Raj Kothapalli, Jim Brooks, Geoff Sonn)

Breast Cancer Biomarker study (Sharon Pitteri and Jafi Lipson)

Stanford Partnered with Duke and Google X on a New “Baseline Study” to Better Understand Human Health

Publications

Gambhir Lab Papers Funded in Part by Canary Foundation

Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker. Ronald JA, Chuang HY, Dragulescu-Andrasi A, Hori SS, Gambhir SS. Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):3068-73. doi: 10.1073/pnas.1414156112. Epub 2015 Feb 23. PMID: 25713388

A Raman-based endoscopic strategy for multiplexed molecular imaging.
Zavaleta CL, Garai E, Liu JT, Sensarn S, Mandella MJ, Van de Sompel D, Friedland S, Van Dam J, Contag CH, Gambhir SS. Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):E2288-97. doi: 10.1073/pnas.1211309110. Epub 2013 May 23. PMID: 23703909

A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle. Kircher MF, de la Zerda A, Jokerst JV, Zavaleta CL, Kempen PJ, Mittra E, Pitter K, Huang R, Campos C, Habte F, Sinclair R, Brennan CW, Mellinghoff IK, Holland EC, Gambhir SS. Nat Med. 2012 Apr 15;18(5):829-34. doi: 10.1038/nm.2721. PMID: 22504484

Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Hori SS, Gambhir SS. Sci Transl Med. 2011 Nov 16;3(109):109ra116. doi: 10.1126/scitranslmed.3003110. PMID: 22089452

Gold nanoparticles: a revival in precious metal administration to patients. Thakor AS, Jokerst J, Zavaleta C, Massoud TF, Gambhir SS. Nano Lett. 2011 Oct 12;11(10):4029-36. doi: 10.1021/nl202559p. Epub 2011 Sep 7. PMID: 21846107

Preclinical evaluation of Raman nanoparticle biodistribution for their potential use in clinical endoscopy imaging. Zavaleta CL, Hartman KB, Miao Z, James ML, Kempen P, Thakor AS, Nielsen CH, Sinclair R, Cheng Z, Gambhir SS. Small. 2011 Aug 8;7(15):2232-40. doi: 10.1002/smll.201002317. Epub 2011 May 24. PMID: 21608124

Early diagnosis of ovarian carcinoma: is a solution in sight? Lutz AM, Willmann JK, Drescher CW, Ray P, Cochran FV, Urban N, Gambhir SS. Radiology. 2011 May;259(2):329-45. doi: 10.1148/radiol.11090563. Review. PMID: 21502390

The fate and toxicity of Raman-active silica-gold nanoparticles in mice. Thakor AS, Luong R, Paulmurugan R, Lin FI, Kempen P, Zavaleta C, Chu P, Massoud TF, Sinclair R, Gambhir SS. Sci Transl Med. 2011 Apr 20;3(79):79ra33. doi: 10.1126/scitranslmed.3001963. PMID: 21508310

Oxidative stress mediates the effects of Raman-active gold nanoparticles in human cells. Thakor AS, Paulmurugan R, Kempen P, Zavaleta C, Sinclair R, Massoud TF, Gambhir SS. Small. 2011 Jan 3;7(1):126-36. doi: 10.1002/smll.201001466. PMID: 21104804

PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide. Nielsen CH, Kimura RH, Withofs N, Tran PT, Miao Z, Cochran JR, Cheng Z, Felsher D, Kjær A, Willmann JK, Gambhir SS. Cancer Res. 2010 Nov 15;70(22):9022-30. doi: 10.1158/0008-5472.CAN-10-1338. Epub 2010 Nov 9. PMID: 21062977

Cancer screening: a mathematical model relating secreted blood biomarker levels to tumor sizes. Lutz AM, Willmann JK, Cochran FV, Ray P, Gambhir SS. PLoS Med. 2008 Aug 19;5(8):e170. doi: 10.1371/journal.pmed.0050170. PMID: 18715113

2-deoxy-2-[F-18]fluoro-D-glucose accumulation in ovarian carcinoma cell lines. Lutz AM, Ray P, Willmann JK, Drescher C, Gambhir SS. Mol Imaging Biol. 2007 Sep-Oct;9(5):260-6. PMID: 17610017

The new Canary Center for Early Cancer Detection at Stanford is the first facility of its kind to bring together scientists from the fields of blood-based diagnostics with molecular imaging diagnostics. We will imagine, invent, and innovate.

Dr. Sanjiv Gambhir
Chair of Radiology, Stanford University & Canary Center at Stanford team leader