MIPS Seminar Series: “Circulating Tumor DNA Biomarkers for Therapy Monitoring and Early Detection”
Shan X. Wang, PhD
Leland T. Edwards Professor in the School of Engineering
Professor of Materials Science & Engineering, jointly of Electrical Engineering, and by courtesy of Radiology (Stanford School of Medicine)
Director, Stanford Center for Magnetic Nanotechnology
Webinar URL: https://stanford.zoom.us/s/93202777468
Dial: +1 650 724 9799 or +1 833 302 1536
Webinar ID: 932 0277 7468
12:00pm – 12:45pm Seminar & Discussion
Inspired by Dr Sam Gambhir, MIPS, Canary Center, and Stanford CCNE have pursued in vivo imaging and in vitro diagnostic tests for cancer therapeutic response or early detection, respectively, over the last 15+ years. Here I present two successful examples based on circulating tumor DNA (ctDNA) targets in plasma, complementary to imaging modalities such as CT and Ultrasound.
We have developed a simple yet highly sensitive assay for the detection of actionable mutational targets such as Epidermal Growth Factor Receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) mutations in the plasma ctDNA from non-small cell lung cancer (NSCLC) patients using giant magnetoresistive (GMR) nanosensors. Our assay achieves lower limits of detection compared to standard fluorescent PCR based assays, and comparable performance to digital PCR methods. In 30 patients with metastatic disease and known EGFR mutation status at diagnosis, our assay achieved 87.5% sensitivity for Exon19 deletion and 90% sensitivity for L858R mutation while retaining 100% specificity; additionally, our assay detected secondary T790M mutation resistance with 96.3% specificity while retaining 100% sensitivity. We re-sampled 13 patients undergoing tyrosine kinase inhibitor (TKI) therapy 2 weeks after initiation to assess response, our GMR assay was 100% accurate in correlation with longitudinal clinical outcome, and the responders identified by the GMR assay had significantly improved progression free survival (PFS) compared to the non-responders. The GMR assay is low cost, rapid, and portable, making it ideal for detecting actionable mutations at diagnosis and non-invasively monitoring treatment response in the clinic.
On another front, we have also developed a highly sensitive and multiplexed assay for the detection of methylated ctDNA targets in plasma samples. Current diagnostic tests for liver cancer in at-risk patients are cumbersome, costly and inaccurate, resulting in a need for accurate blood-based tests. By devising a Layered Analysis of Methylated Biomarkers (LAMB) from the relevant big data, we have discovered a set of DNA targets in the blood that accurately detects liver cancer in these at-risk patients. This set of methylated targets was found by analyzing the genetic information of 3411 liver cancer patients and 1722 healthy people. Our results could lead to clinical adoption of liquid biopsy tests for liver cancer surveillance in high-risk populations and the development of blood tests for other cancers.
Prof. Wang directs the Center for Magnetic Nanotechnology and is a leading expert in biosensors, information storage and spintronics. His research and inventions span across a variety of areas including magnetic biochips, in vitro diagnostics, cancer biomarkers, magnetic nanoparticles, magnetic sensors, magnetoresistive random access memory, and magnetic integrated inductors. He has over 300 publications, and holds 65 issued or pending patents in these and interdisciplinary areas. He was named an inaugural Fred Terman Fellow, and was elected a Fellow of the Institute of Electrical and Electronics Engineers (IEEE) and a Fellow of American Physical Society (APS) for his seminal contributions to magnetic materials and nanosensors. His team won the Grand Challenge Exploration Award from Gates Foundation (2010), the XCHALLENGE Distinguished Award (2014), and the Bold Epic Innovator Award from the XPRIZE Foundation (2017).
Dr. Wang cofounded three high-tech startups in Silicon Valley, including MagArray, Inc. and Flux Biosciences, Inc. In 2018 MagArray launched a first of its kind lung cancer early diagnostic assay based on protein cancer biomarkers and support vector machine (SVM). In 2019, Flux Biosciences launched a human trial to offer at-home testing of fertility based on hormones and magneto-nanosensors. Through his participation in the Center for Cancer Nanotechnology Excellence (as co-PI of the CCNE) and the Joint University Microelectronics Program (JUMP), he is actively engaged in the transformative research of healthcare and is developing emerging memories for energy efficient computing.
Hosted by: Katherine Ferrara, PhD
Sponsored by: Molecular Imaging Program at Stanford & the Department of Radiology