MECHANO-METABOLIC SIGNATURES OF METASTATIC DISEASE

Abstract

Traditionally biological or genetic mutations have been used to distinguish cancer from normal tissues and to stratify cancers into molecular subtypes, resulting in successful targeted therapies. In a similar way, the cancer mechanical phenotype holds significant promise as a potential biomarker as cancers show altered biophysical phenotypes at the cellular and tissue length scales. However, translating these biophysical traits into cellular function or physiological traits as druggable targets remains challenging. Recent work has demonstrated that modulation of the microenvironment stiffness can promote metabolic rewiring which in turn is linked to cancer invasion. Metabolic plasticity is known to be a “hallmark of cancer,” as cancer cells must undergo metabolic evolution to survive or adapt to new organ microenvironments. Additionally, the tumor metabolic microenvironment regulates the efficacy of immunotherapies. Therefore, a promising nascent research direction is the investigation of the balance between tissue mechanics and metabolism, its potential dysregulation during metastatic progression, and its role in response to cancer treatments. The overall goal of this research is to decipher the interplay of cancer mechanobiology and metabolism in metastatic disease.