TY - JOUR
T1 - Cancer as a biophysical disease
T2 - Targeting the mechanical-adaptability program
AU - Nguyen, Ly T.S.
AU - Jacob, Mark Allan C.
AU - Parajón, Eleana
AU - Robinson, Douglas N.
N1 - Publisher Copyright:
© 2022 Biophysical Society
PY - 2022/10/4
Y1 - 2022/10/4
N2 - 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.
AB - 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.
KW - actin crosslinkers
KW - cancer progression
KW - cortical mechanics
KW - mechanical adaptability
KW - myosin II
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U2 - 10.1016/j.bpj.2022.04.039
DO - 10.1016/j.bpj.2022.04.039
M3 - Review article
C2 - 35505610
AN - SCOPUS:85130498316
SN - 0006-3495
VL - 121
SP - 3573
EP - 3585
JO - Biophysical journal
JF - Biophysical journal
IS - 19
ER -