Cambridge Healthtech Instituteの第8回年次会議
Liquid Biopsy for Disease Management
2023年8月21 - 22日、EDT（米国東部標準時）
Scientific Advisory Board
Stuart S. Martin, PhD, Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center,
University of Maryland School of Medicine
Sunitha Nagrath, PhD, Associate Professor, Chemical Engineering; Co-Director, Single Cell Analysis Core,
Rogel Cancer Center BioInterfaces Institute, University of Michigan
Steven A. Soper, PhD, Professor & Director, CBM2 Precision Medicine, Chemistry & Mechanical Engineering,
University of Kansas, Lawrence
Registration and Morning Coffee7:15 am
NEW TECHNOLOGIES FOR LIQUID BIOPSY ANALYSES
Impact of NCI Funding in the Advancement of Technologies for Liquid Biopsies
Miguel R. Ossandon, PhD, Program Director, Cancer Diagnosis Program, Diagnostic Biomarkers and Technology Branch (DBTB), Division of Cancer Treatment and Diagnosis National Cancer Institute, NIH
Hypothesis-driven research; money-driven research. This talk will be focused on the impact of technology research programs at the NCI, and how these NCI initiatives support the development and translation of liquid biopsy technologies. Questions discussed in this talk would include: how funding can direct research priorities, and what are the challenges in the various stages of development, for liquid biopsy technology, related to funding opportunities.
Extracellular Vesicle (EV) Analytics: High-Throughput Measurement of Single Nanoparticles with Single-Molecule Resolution
John Nolan, PhD, Professor, The Scintillon Institute
EVs are released by all cells and carry molecular cargo that can be used to assess the identity and state of their cell of origin, making them attractive targets for liquid biopsy. However, EVs are also very small, heterogeneous, and difficult to measure, posing challenges to their rigorous and reproducible measurement. Recent advances in instruments, reagents, and assays are enabling the quantitative analysis of EVs and their cargo with high throughput, sensitivity, and molecular resolution.
Urinary Extracellular Vesicle-Derived Biomarkers for Bladder Cancer
Mei He, PhD, Assistant Professor, Pharmaceutics, University of Florida, Gainesville
Urinary extracellular vesicles (EVs) are great resources for multi-omic investigation on specific biomarkers for diagnostic and prognostic analysis of MIBC. We identified urinary EV-based molecular fingerprints for detection of MIBC and predicting their therapeutic response. The ability to predict best responses to NAC could significantly improve oncological outcomes and decreased effects on patients’ quality of life.
Coffee Break in the Exhibit Hall with Poster Viewing10:00 am
Acoustofluidic Technologies for the Manipulation of Cells and Extracellular Vesicles
Tony Jun Huang, PhD, Professor, Mechanical Engineering & Materials Science MEMS, Duke University
In this talk, I summarize our lab’s recent progress in this exciting field and highlight the versatility of acoustofluidic tools for biomedical applications through many unique examples, ranging from the development of high-purity, high-yield methods for the separation of circulating biomarkers such as small extracellular vesicles (sEVs) and circulating tumor cells (CTCs), to our newly developed harmonic acoustics for a non-contact, dynamic, selective (HANDS) particle manipulation platform, which enables the reversible assembly and disassembly of cells. These acoustofluidic devices can precisely manipulate objects across 7 orders of magnitude (from a few nanometers to a few centimeters). Thanks to these favorable attributes (e.g., versatility, precision, and biocompatibility), acoustofluidic devices harbor enormous potential in becoming a leading technology for a broad range of applications, playing a critical role for translating innovations in technology into advances in biology and medicine.
Quantification of Extracellular Vesicle Subpopulations for Early Diagnosis of Solid Tumors
HsianRong Tseng, PhD, Professor, Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, UCLA
The UCLA Liquid Biopsy Laboratory has developed an IVD test that utilizes extracellular vesicles (EVs) to detect systemic disease burden with great sensitivity. This novel test can quantify tumor EVs using less than 1mL plasma and a 2-hour workflow, by utilizing a proprietary Click Chemistry-mediated EV enrichment followed by downstream EV quantification using PCR. Our first clinical test is specifically designed to distinguish hepatocellular carcinoma (HCC) from at-risk liver cirrhosis, and has been validated through a phase II biomarker study.
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:15 pm
Session Break1:15 pm
BRIDGING LIQUID BIOPSY TO IMPROVE CANCER TREATMENT
The Metastatic Spread of Breast Cancer Accelerates during Sleep
Zoi Diamantopoulou, PhD, Marie Sklodowska-Curie Postdoctoral Fellow, Molecular Oncology Lab, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich
The metastatic spread of cancer is achieved by the haematogenous dissemination of CTCs. However, the temporal dynamics dictating the generation of metastasis-competent CTCs are largely uncharacterised and it is often assumed that CTCs are constantly shed from growing tumours. Here I will present data showing a striking and unexpected pattern of CTC generation dynamics, highlighting that most spontaneous CTC intravasation events occur during sleep.
- Breast cancer spreads during sleep
- Timing of biopsy collection can be critical for an accurate cancer diagnosis
- Chronotherapy could lead to more effective disease management in cancer patients?
Liquid Biopsy for Rapid Treatment Selection in Cancer Patients
Pauline Funchain, MD, Medical Oncologist, Hematology & Medical Oncology, Cleveland Clinic Foundation
Using a plasma-based BRAF mutation detection system allowed for rapid detection of BRAF mutation in a case of metastatic melanoma, enabling same-day initiation of targeted therapy without the need for invasive biopsy. This case involved a hospitalized 53-year-old male with rapidly deteriorating clinical status due to extensive melanoma metastases, and BRAF mutation status was unknown. Targeted treatment with dabrafenib and trametinib resulted in swift improvement, allowing for discharge within a week and significant clinical improvement over the following weeks. Harnessing this type of technology can improve outcomes in urgent clinical situations where timely decision-making is critical.
The Roles of Drug Resistance and Membrane Lipid Structure on Cell Mechanotransduction and Survival in Advanced Colorectal Cancer
Michael R. King, PhD, J. Lawrence Wilson Chair, Biomedical Engineering, Vanderbilt University
Our laboratory has found that colorectal cancer (CRC) cells resistant to oxaliplatin chemotherapy become more sensitive to TRAIL-mediated cell death. This increased sensitivity is due to augmented death receptor 4 (DR4) localization within tightly packed, cholesterol-enriched regions in the cell membrane known as lipid rafts. This mechanism of DR4 translocation into lipid rafts within oxaliplatin-resistant cells is found to be through increased palmitoylation of DR4. In the circulation, these cells experience activation of the mechanosensitive ion channel Piezo1, causing an influx of calcium that can be exploited with novel therapies.
Refreshment Break in the Exhibit Hall with Poster Viewing3:05 pm
Circulating Tumor Cell Clusters as Harbingers and Avatars of Metastasis
Gisela Esta Sterneck, PhD, Senior Investigator, Lab of Cell & Developmental Signaling, NIH NCI
Circulating tumor cell clusters (CTCs) are significantly associated with poor prognosis due to enhanced seeding of metastases compared to single cells, suggesting that cell-cell adhesion mechanisms are potential targets for the prevention and treatment of metastases. Using preclinical mouse models and a liquid 3D cell culture paradigm, we recently discovered that the pro-inflammatory prostaglandin signaling pathway stabilizes epithelial cadherin adhesion proteins and can be targeted with several clinically approved pharmacological agents.
Microfluidic Capture of CTC Heterogeneity and Isolation/Culture of Highly Metastatic CTCs
Xiaoming Shawn He, PhD, Professor, Bioengineering, University of Maryland College Park
We developed a novel microfluidic device for not only efficient capture but also controlled release of heterogenous circulating tumor cells (CTCs) with high viability. Capturing the CTC heterogeneity was found to greatly enhance the CTC culturability in vitro for their further use and analysis. Moreover, we developed a novel one-cell culture technology to isolate and culture the rare metastatic subpopulation of CTCs as a potential target to combat cancer metastasis.
Sponsored Presentation (Opportunity Available)5:00 pm
Wine and Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing5:15 pm
Close of Day6:30 pm
Registration Open7:15 am
Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussions page on the conference website for a complete listing of topics and descriptions.
LIQUID BIOPSY FOR PRECISION MEDICINE
Liquid Biopsy Analysis in Patients with Brain Metastasis
Min Yu, MD, PhD, Associate Professor, Department of Pharmacology, University of Maryland School of Medicine
Circulating tumor cells (CTCs) and cell free DNA (cfDNA) are considered types of liquid biopsy for cancer diagnosis and monitoring. In this study, we analyzed both CTCs and cfDNA from a small cohort of cancer patients with brain metastasis and also compared with the single cell transcriptome from the brain metastasis. The goal is to evaluate whether CTCs or cfDNA can be used to infer brain metastasis prediction or signature.
Single-Cell Analysis of Circulating Tumor Cells for Precision Medicine
Sunitha Nagrath, PhD (Fellow of AIMBE) Professor of Chemical Engineering Professor of Biomedical Engineering Co-Director, Liquid Biopsy Shared Resources, Rogel Cancer Center University of Michigan
Circulating tumor cells (CTCs) represent an especially aggressive subset of cancer cells, capable of causing metastasis and progressing the disease. Due to the genetic instability and dynamic changes a tumor undergoes throughout treatment, real-time CTC monitoring of tumor evolution could help continually optimize a patient’s treatment plan, improving patient outcome. A workflow for rapid single cell profiling of CTCs for simultaneous gene expression and mutation detection will be presented. The single-cell resolution enables the early detection of emerging rare clones that could lead to therapeutic resistance from a routine blood draw, allowing for more predictive analysis of targeted therapy response.
FIRESIDE CHAT: Collaborating to Lay the Groundwork for Molecular Residual Disease as an Early Endpoint in Solid Tumors
Lauren Leiman, Executive Director, BLOODPAC Consortium
- How BLOODPAC works collaboratively to develop and execute a strategic plan for MRD implementation
- BLOODPAC's progress in establishing an MRD lexicon, determining recommended data elements, and developing clinical protocols
- The value of data curation and a data commons in accelerating research
- Next steps in moving towards clinical use of MRD
Sponsored Presentation (Opportunity Available)10:00 am
Coffee Break in the Exhibit Hall with Poster Viewing10:30 am
Transition to Plenary Panel Discussion11:15 am
PLENARY SESSION Co-Organized by PMC
Policy and Practice Strategies to Address the Clinical Practice Gaps Affecting the Implementation of Personalized Medicine in Cancer Care
Daryl Pritchard, PhD, Senior Vice President, Science Policy, Personalized Medicine Coalition
Many oncology patients who are eligible to receive high-value personalized treatments do not. Despite a lengthy history of targeted treatment availability in advanced non-small cell lung cancer (aNSCLC), a recent study found that 644 of every 1,000 newly diagnosed aNSCLC patients (64.4%) did not receive a personalized treatment due to clinical practice gaps in the delivery of precision oncology.
- What are the clinical practice and policy challenges related to diagnostic testing and the delivery of appropriate targeted therapies leading to a failure of patients to receive precision oncology strategies?
- What impact does each clinical practice gap have on the population-level delivery of precision oncology?
- How can we optimize biomarker testing and treatment decision-making to help best address clinical practice gaps?
- What policies and practices can help assure optimal and equitable delivery of appropriate high-value personalized medicines?
Anthony N. Sireci, MD, Senior Vice President, Clinical Biomarkers & Diagnostics Division, Loxo Oncology, Inc.
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:30 pm
Close of Liquid Biopsy for Disease Management Conference1:30 pm
Recommended Dinner Short Course6:00 pm
SC2: Translating CTCs, ctDNA, and Exosomes for Clinical Use
*Separate registration required. See short courses page for details.
2023 Conference Programs