Cancer as a biophysical disease: Targeting the mechanical-adaptability program

Biophys J. 2022 Oct 4;121(19):3573-3585. doi: 10.1016/j.bpj.2022.04.039. Epub 2022 May 3.


With the number of cancer cases projected to significantly increase over time, researchers are currently exploring "nontraditional" research fields in the pursuit of novel therapeutics. One emerging area that is steadily gathering interest revolves around cellular mechanical machinery. When looking broadly at the physical properties of cancer, it has been debated whether a cancer could be defined as either stiffer or softer across cancer types. With numerous articles supporting both sides, the evidence instead suggests that cancer is not particularly regimented. Instead, cancer is highly adaptable, allowing it to endure the constantly changing microenvironments cancer cells encounter, such as tumor compression and the shear forces in the vascular system and body. What allows cancer cells to achieve this adaptability are the particular proteins that make up the mechanical network, leading to a particular mechanical program of the cancer cell. Coincidentally, some of these proteins, such as myosin II, α-actinins, filamins, and actin, have either altered expression in cancer and/or some type of direct involvement in cancer progression. For this reason, targeting the mechanical system as a therapeutic strategy may lead to more efficacious treatments in the future. However, targeting the mechanical program is far from trivial. As involved as the mechanical program is in cancer development and metastasis, it also helps drive many other key cellular processes, such as cell division, cell adhesion, metabolism, and motility. Therefore, anti-cancer treatments targeting the mechanical program must take great care to avoid potential side effects. Here, we introduce the potential of targeting the mechanical program while also providing its challenges and shortcomings as a strategy for cancer treatment.

Keywords: actin crosslinkers; cancer progression; cortical mechanics; mechanical adaptability; myosin II.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin
  • Actins* / metabolism
  • Filamins
  • Humans
  • Myosin Type II / metabolism
  • Neoplasms* / pathology
  • Tumor Microenvironment


  • Actins
  • Filamins
  • Actinin
  • Myosin Type II