The Problem Circulating tumor cells (CTCs) are shed from solid tumors into the peripheral blood system during cancer progression. CTCs can be used as a “liquid biopsy”, enabling rapid and real-time tumor monitoring with minimal risk as compared to traditional tissue biopsy methods. However, CTCs are an extremely rare cell population–as few as one per billion blood cells–requiring specialized technology capable of high efficiency and high purity CTC isolation. Once these cells are isolated, novel strategies are needed to fully characterize and understand their phenotype, and how it correlates with the original tumor.
The Approach Study of CTCs has been hampered by lack of high-purity samples which capture to full breadth of cancer cell heterogeneity. To address this need, I co-designed the geometrically enhanced differential immunocapture (GEDI) platform for size- and antigen-based isolation of CTCs from whole blood samples. we demonstrated that this combinatorial strategy ~40% higher capture specficity and purity than contemporary immunocapture methods . I also characterized a toolbox of reversible biotin analogues for controlled non-enzymatic release of live CTCs from GEDI microdevices for downstream off-chip analysis. In collaboration with Prof. James Hicks, I developed a strategy for high efficiency CTC isolation and elution, followed by single-cell copy number variation (CNV) analysis . We also demonstrated that CTCs could be assessed in vitro for functional response to taxane chemotherapy . The GEDI platform was subsequently used to quantify drug-target engagement in patient CTCs as a primary endpoint of the TAXYNERGY/NCT01718353 Phase II clinical trial .
Project Funding Alfred P. Sloan Foundation Graduate Research Fellowship (2008), NSF Graduate Research Fellowship (2009), Cornell PS-OC Young Investigator’s Award (2012)
1. Gleghorn, J.P., Pratt, E.D., Denning, D., Liu, H., Bander, N.H., Tagawa, S.T., Nanus, D.M., Giannakakou, P.A., and Kirby, B.J. (2010). Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody. Lab on a Chip 10, 27–29.
2. Pratt, E.D., Stepansky, A., Hicks, J., and Kirby, B.J. (2014). Single-cell copy number analysis of prostate cancer cells using GEDI microdevices. Analytical Chemistry 88, 11013–11017.
3. Kirby, B.J., Jodari, M., Loftus, M.S., Pratt, E.D., Gakhar, G., Gleghorn, J.P., Santana, S.M., Liu, H., Smith, J.P., and Navarro, V.N. et al. (2012). Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS ONE 7.
4. Antonarakis, E.S., Tagawa, S.T., Galletti, G., Worroll, D., Ballman, K., Vanhuyse, M., Sonpavde, G., North, S., Albany, C., and Tsao, C.-K. et al. (2017). A randomized non-comparative phase ii trial of early switch from docetaxel to cabazitaxel or vice versa, with integrated biomarker analysis, in men with chemotherapy-naïve metastatic castration-resistant prostate cancer. Journal of Clinical Oncology.
5. Pratt, E.D., Huang, C., Hawkins, B.G., Gleghorn, J.P., and Kirby, B.J. (2011). Rare cell capture in microfluidic devices. Chemical Engineering Science 66, 1508–1522.