Isolation of Rare Circulating Tumor Cells in Cancer Patients by Microchip Technology Toner, et al. 2007 Stephanie Bachar Matt Luchette
Background: Circulating Tumor Cells CTCs: tumor cells shed into the blood stream Motivation for detection Study biology of metastasis Diagnose, detect, monitor cancer in patients without invasive biopsy The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites Y Shiozawa, A M Havens, K J Pienta and R S Taichman
Motivation for the “CTC-Chip” Shortcomings prior to “CTC-Chip” Accuracy: 20-60% Purity: 0.1% Non-viable cells Photoacoustic detection of CTCs. Viator lab at University of Missouri http://web.missouri.edu/~viatorj/tumor.htm
How to use the “CTC Chip" Flow sample through CTC Chip EpCAM coated microposts Verify with markers Pressure Control Blood on Rocker CTC Chip Toner 2007 EpCAM Non-CTCs CTCs Micropost CD45 Cytokeratin
Instrument Design: in silico Maximize CTCs detected Flow Velocity Shear Force Vary micropost characteristics Theoretical capture efficiency of 65% Toner 2007
Capture purity per type of cancer Laboratory Results 1 target cell/10^9 blood cells Purity of capture ~60% (competitors = 0.1%) Efficiency of capture ~65% (competitors = 35%) Captured cells were viable and could be further manipulated Capture purity per type of cancer Toner 2007
Clinical Results Identified CTCs in 99% cancer pts (competitors = 20-60%) no false positives Change in number of CTCs correlated with clinical path No pre-processing required Change in CTCs captured per mL (red) with lung cancer patient mirrors change in tumor size (blue) Toner 2007
Concerns and next steps How cells used afterwards? How to mass produce chips? Financially viable? How reliable is EpCAM as a caner cell marker? FDA approval Paper tree-branch glucose and protein assay for urine technologyreview.com
Recap/Applications New diagnostic and prognostic tool for cancer patients Provide alternative to biopsies for areas with low resources Use to isolate and further study CTCs MRI of 67-year old patient with pancreatic cancer with the pancreatic tumor indicated imagingeconomics.com
Works Cited --imagingeconomics.com --technologyreview.com --http://web.missouri.edu/~viatorj/tumor.htm --The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites Y Shiozawa, A M Havens, K J Pienta and R S Taichman