Beyond Tissue Stiffness and Bioadhesivity: Advanced Biomaterials to Model Tumor Microenvironments and Drug Resistance.

Resistance to chemotherapy and pathway-targeted therapies poses a major problem in cancer research. While the fields of tumor biology and experimental therapeutics have already benefited from ex vivo preclinical tissue models, these models have yet to address the reasons for malignant transformations and the emergence of chemoresistance. With the increasing number of ex vivo models poised to incorporate physiological biophysical properties, along with the advent of genomic sequencing information, there are now unprecedented opportunities to better understand tumorigenesis and to design therapeutic approaches to overcome resistance. Here we discuss that new preclinical ex vivo models should consider - in addition to common biophysical parameters such as matrix stiffness and bioadhesivity - a more comprehensive milieu of tissue signaling, nuclear mechanics, immune response, and the gut microbiome.