Mechanical cues in tumor microenvironment on chip

Mechanical cues from the tumor microenvironment (TME) can influence cell behaviors and have been indicated to play a pivotal role in tumor initiation, progression, and metastasis. The integration of microfluidics technologies, bioelectronics, and tissue engineering approaches have allowed the development of various in-vitro TME on-chip models. These models recapitulate and systematically simplify the intricate mechanical characteristics and interactions within tumors, enabling the study of the metastatic process with unprecedented detail. In this review, we will focus on shear flow, confinement, and stiffness and elucidate their mechanotransduction processes that contribute to the onset of metastatic cascade. Finally, novel Cancer-on-chip models are discussed along with an outlook on challenges and future perspectives of this emerging technology. •Three physical cues from the tumor microenvironment (TME) and their relationship to mechanosensing will be reviewed.•Current engineering approaches to generating the mechanical cues of the TME and in-vitro models of the TME are introduced.•Cancer-on-chip (CoC) devices integrating biochemical and physical cues within microfluidic devices are discussed.•Potential clinical applications and future directions for microfluidics and CoC are presented.