Abstract

Solid tumors, such as sarcoma, stiffen as they grow in a host’s normal tissue. Stiffening is caused by an increase in the structural components of the tumor, particularly in the density of cancer cells, stromal cells, and the extracellular matrix fibers. As a result, the tumor microenvironment poses major physiological barriers to the effective delivery of drugs, which explains in large part why clinically approved cancer therapies often fail. Failure of standard cancer therapies has led to the introduction of a new era of personalized, patient-specific treatments. The basis of these treatments is the identification of biomarkers that characterize the state of a tumor. In this project, Atomic Force Microscopy-AFM will be used to assess unique NanoMechanical FingerPrints of sarcoma. The AFM-based NanoMechanical FingerPrints will aim to identify the nanomechanical properties of sarcoma cells in vitro and predict or monitor the patient’s response to cancer related treatments. Successful completion of the project will reveal the mechanism of different NanoMechanical FingerPrints for sarcoma and will enable the development of predictive biomarkers, the first that exploit tumor mechanics, with easy transfer to the clinic.

This project propose the use of state-of-the-art AFM techniques for the development of a NanoMechanical Biomarker, which will quantify the NMFP of sarcoma. This biomarker will aim to:

(i) identify the nanomechanical properties of sarcoma cells in vitro,

(ii) predict the patient’s response to chemotherapy (response predictions) and

(iii) monitor treatment outcomes, in the case of novel approaches that target tumor mechanical properties (e.g., TME normalization). In this project, we propose to test the hypothesis that AFM can identify unique and novel cancer NMFP that can be used for treatment prediction and monitoring.