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Cancer

Microtubule protein level predicts drugs’ effectiveness against brain cancer cells

Lab study shows that drugs like paclitaxel are more effective against glioblastoma cells with higher levels of tubulin

by Cici Zhang, special to C&EN
September 14, 2019 | A version of this story appeared in Volume 97, Issue 36

 

Immunofluorescent micrograph of microtubules (spindles) comprising the mitotic apparatus active during cell division.
Credit: Dr. Gerald Schatten/Science Source
The effectiveness of some cancer drugs depends on levels of the protein in cell microtubules (shown).

Certain chemotherapy drugs block cancer cell division by targeting microtubules—structural polymers that are made of a protein called tubulin and are critical for cell division and other functions. Such microtubule-targeting agents (MTAs) are promising drug candidates against glioblastoma, an aggressive type of brain cancer, but they have not reached the clinic, in part because of highly variable results in the lab. Now, researchers have found one reason why MTAs do not stop the growth of all glioblastoma cells: the levels of tubulin in these cells affect their susceptibility to MTAs (ACS Pharmacol. Transl. Sci. 2019, DOI: 10.1021/acsptsci.9b00045). Lenka Munoz of the University of Sydney and her team measured tubulin levels in 15 glioblastoma cell lines. Then they tested four MTAs that can potentially cross the blood-brain barrier—colchicine, nocodazole, tivantinib, and CMPD1—against the cell lines. In all cases, cells with higher tubulin levels were more susceptible to the drugs. Also, cell lines that survived treatment with three other MTAs had tubulin levels as much as 20% lower than lines that didn’t survive. Why cells have different levels of tubulin is not yet known, Munoz says. But if confirmed in animal models, the results could pave the way for personalized therapy when using MTAs to treat brain cancer.

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