Principal Investigator

Ashutosh
Agarwal
Awardee Organization

University Of Miami School Of Medicine
United States

Fiscal Year
2022
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

A comprehensive liquid biopsy platform for detection and prognostication in early stage breast cancer

We seek to develop robust platforms for capturing, enumerating and analyzing circulating tumor cells and associated cancer cells from the blood of cancer patients. We will leverage our previously developed precisely engineered microfilter platform that allows effective separation and collection of viable CTC from patient blood. In parallel, we have developed novel imaging methods perfectly suited for rapid analyses for circulating tumor cells, clusters and associated cancer cell subtypes (such as Cancer Associated Fibroblasts, or CAF). We propose to integrate these two novel technologies to create a robust diagnostic tool for clinical pathology as well as basic research that enables capture, enumeration, and analyses of circulating tumor cells and associated cancer cells. Our multidisciplinary team proposes the following Specific Aims: 1) Build and validate the technology to rapidly acquire CTC/CAF images using Fourier Ptychographic Microscopy and evaluate the images with a deep learning algorithm 2) Evaluation of the integrated platform for using CTC/CAF in predicting recurrence/survival in early stage breast cancer patients For these studies in early stage breast cancer, we have robust collaborations with industry partners in Circulogix Inc (Microfilter technology for cell capture), ClearBridge Inc. (FPM imaging of the microfilter surface), and Google Software (Deep learning algorithm for analyzing FPM images of microfilter). The ability to reliably and rapidly detect and analyze CTC and associated cancer cells in early stage breast cancer patients would deliver a major new tool for oncology research, a platform for screening of novel drugs, and a critical advance in precision cancer management.

Publications

  • Zhou H, Watson M, Bernadt CT, Lin SS, Lin CY, Ritter JH, Wein A, Mahler S, Rawal S, Govindan R, Yang C, Cote RJ. AI-guided histopathology predicts brain metastasis in lung cancer patients. The Journal of pathology. 2024 May;263(1):89-98. Epub 2024 Mar 4. PMID: 38433721
  • Besser RR, Bowles AC, Alassaf A, Carbonero D, Claure I, Jones E, Reda J, Wubker L, Batchelor W, Ziebarth N, Silvera R, Khan A, Maciel R, Saporta M, Agarwal A. Enzymatically crosslinked gelatin-laminin hydrogels for applications in neuromuscular tissue engineering. Biomaterials science. 2020 Jan 21;8(2):591-606. PMID: 31859298
  • Besser RR, Bowles AC, Alassaf A, Carbonero D, Maciel R, Saporta M, Agarwal A. A Chemically Defined Common Medium for Culture of C2C12 Skeletal Muscle and Human Induced Pluripotent Stem Cell Derived Spinal Spheroids. Cellular and molecular bioengineering. 2020 Jun 10;13(6):605-619. doi: 10.1007/s12195-020-00624-1. eCollection 2020 Dec. PMID: 33281990
  • Mayo V, Bowles AC, Wubker LE, Ortiz I, Cordoves AM, Cote RJ, Correa D, Agarwal A. Human-derived osteoblast-like cells and pericyte-like cells induce distinct metastatic phenotypes in primary breast cancer cells. Experimental biology and medicine (Maywood, N.J.). 2021 Apr;246(8):971-985. Epub 2020 Nov 19. PMID: 33210551
  • Shen C, Rawal S, Brown R, Zhou H, Agarwal A, Watson MA, Cote RJ, Yang C. Automatic detection of circulating tumor cells and cancer associated fibroblasts using deep learning. Scientific reports. 2023 Apr 7;13(1):5708. PMID: 37029224
  • Yang YP, Giret TM, Cote RJ. Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities. Cancers. 2021 May 31;13. (11). PMID: 34072844
  • Liang M, Yang C. Implementation of free-space Fourier Ptychography with near maximum system numerical aperture. Optics express. 2022 Jun 6;30(12):20321-20332. PMID: 36224781