2019 SYNDICATE Participants
The Synthetic Biomarkers for Detection of Cancers at Incipient and Early Stages (SYNDICATE) Think Tank Meeting, was held July 29-30, 2019 and was hosted by the Division of Cancer Prevention (DCP), and co-chaired by Dr. Sangeeta Bhatia, Massachusetts Institute of Technology, and Dr. Sam Gambhir, Stanford University.
Introduction: Early detection of cancers is an important component of the battle against cancer and holds significant promise. Biomarkers for early detection of cancer using non-invasive or minimally invasive methods are primarily being developed from a broad range of distinct, naturally occurring endogenous biomarkers such as cell-free nucleic acids (DNA, mRNA, lncRNA, miRNA), peptides, proteins, metabolites, exosomes and circulating tumor cells that are shed by tumors or released from dying cancer cells. Although progress is being made for both molecular biomarkers and in vivo imaging biomarkers, there are fundamental technical and biological challenges that often limit the development of biomarkers (e.g., very low concentrations in the circulation at the earliest stages of tumor development, tumor heterogeneity, secretion by normal cells, rapid degradation both in vivo and ex vivo).
The use of engineered synthetic biomarkers (signals not normally made and are being forced to make) with built-in cancer-reactive modules is an exciting “out of the box” approach for detection of incipient and early-stage cancers non-invasively in blood or urine. It is a nascent area, but synthetic biomarkers have the potential to overcome the limitations of endogenous products and can also be designed to gauge the malignant potential of a tumor, which can assist in comprehending whether a lesion is clinically meaningful or not. Another potential application is the use of optic probes for imaging the locations of cancer cells. There are reports of exogenously administered non-immunogenic, tumor-penetrating and activity-based probes that can produce synthetic biomarkers in murine models and their translational potential for use in humans need to be explored.
Purpose of the meeting: To review the current status of synthetic biomarkers and discuss the challenges in development of the biomarkers, translation of promising synthetic tools safely from preclinical models to humans, development of new tools, explore combination with endogenous biomarkers, use as companion diagnostics, patient safety, and a variety of other pertinent topics.
Highlights of the meeting: The meeting was structured around three main sessions: Development of Synthetic Biomarkers for Early Detection of Cancer; Translational Opportunities and Challenges; and Clinical Needs and Applications for Early Detection of Cancers. An eclectic mix of enthusiastic leaders from a variety of disciplines (engineering, biology, clinical) engaged in a highly interactive, informative and stimulating discussion for almost two days.
The state of the science talk, delivered by Drs. Bhatia and Gambhir, provided a comprehensive view of some promising technologies and synthetic biomarkers and included a vision for precision health through integrated diagnostics: identify/image/intervene in a personalized way. The short talks and in-depth discussions in each of the three sessions included how to develop and use synthetic biomarker technologies for amplification of signals (biochemical, immune cells, microenvironment, microbes etc.), the much needed biological knowledge of early cancer pathogenesis, model systems that can be used, role of mathematical modeling and artificial intelligence, imaging, multimodal technologies (image and biomarker), multiplexing of probes, as well as some futuristic dreams. Specific cancer types were discussed with a focus on what was the “interception” opportunity for each cancer, where to start and when it could be integrated with advanced medical devices for proximal sampling. In summary, there is a need for early conversations between the engineers, biologists and clinicians to shape the development of these technologies/synthetic biomarkers, have a better understanding of the clinical needs, the types of populations that may benefit, designing pragmatic trials etc. The synthetic biomarker research community may also consider paths that support regulatory and economic innovation.
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