Abstract

The re-emergence of resistant cancer cells after initial therapy is one of the great unsolved, and deadly, problems in oncology, and a fundamental problem of evolution under stress. This project is aimed at understanding, from general principles of physics, ecology, and biology, why recurrence of resistant cancer cells seems to be a universal phenomenon in cancer. We believe that evolution in small, stressed habitats is the key to the rapid and inevitable re-emergence of resistance. The physical technology that drives this Project uses microfabrication of tiny, stressed habitats to test these Ideas. Modern techniques of physical probes, genomics, proteomics and nanotechnology will allow us to analyze the evolutionary path of these emergent resistant cells.

Public Health Relevance

Perhaps the evolution of resistance in cancer is something we are making worse and ultimately more lethal with our present treatment of cancer. We hope that by truly understanding how resistance evolves, we may develop new therapies which control cancer to the point where it is survivable, if not cured.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143803-05
Application #
8535630
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (O1))
Program Officer
Franca-Koh, Jonathan C
Project Start
2009-09-28
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$2,479,751
Indirect Cost
$553,486

  Institution

Name
Princeton University
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544

  Publications

Chalfin, Heather J; Kates, Max; van der Toom, Emma E et al. (2018) Characterization of Urothelial Cancer Circulating Tumor Cells with a Novel Selection-Free Method. Urology 115:82-86
de Groot, Amber E; Pienta, Kenneth J (2018) Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages. Oncotarget 9:20908-20927
Wu, Amy; Liao, David; Kirilin, Vlamimir et al. (2018) Cancer dormancy and criticality from a game theory perspective. Cancer Converg 2:1
van der Toom, Emma E; Axelrod, Haley D; de la Rosette, Jean J et al. (2018) Prostate-specific markers to identify rare prostate cancer cells in liquid biopsies. Nat Rev Urol :
Valkenburg, Kenneth C; de Groot, Amber E; Pienta, Kenneth J (2018) Targeting the tumour stroma to improve cancer therapy. Nat Rev Clin Oncol 15:366-381
Chalfin, Heather J; Glavaris, Stephanie A; Malihi, Paymaneh D et al. (2018) Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms. J Urol 199:1494-1501
Maley, Carlo C; Aktipis, Athena; Graham, Trevor A et al. (2017) Classifying the evolutionary and ecological features of neoplasms. Nat Rev Cancer 17:605-619
Piotrowski-Daspit, Alexandra S; Simi, Allison K; Pang, Mei-Fong et al. (2017) A 3D Culture Model to Study How Fluid Pressure and Flow Affect the Behavior of Aggregates of Epithelial Cells. Methods Mol Biol 1501:245-257
Parsana, Princy; Amend, Sarah R; Hernandez, James et al. (2017) Identifying global expression patterns and key regulators in epithelial to mesenchymal transition through multi-study integration. BMC Cancer 17:447
Decker, A M; Cackowski, F C; Jung, Y et al. (2017) Biochemical Changes in the Niche Following Tumor Cell Invasion. J Cell Biochem 118:1956-1964

Showing the most recent 10 out of 105 publications