Trending with Impact: Basal Cell Bladder Cancer and MEK Inhibitors

For patients with basal cell bladder cancer, researchers in this study identify MEK inhibitors as a viable therapeutic option.

3d Illustration - Bladder cancer cells
3d Illustration – Bladder cancer cell

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“Basal bladder cancer is frequently clinically aggressive and has the worst overall prognosis [3], and thus, additional therapeutic options for these tumors would be highly clinically relevant.”

In this paper published by Oncotarget, researchers from the University of Michigan conducted a study emphasizing the importance of 3D culture screenings versus 2D, and the use of MEK inhibitors to target basal cell bladder cancer. This paper concludes that basal cell bladder cancer cells are significantly more receptive to MEK inhibitors than the other drug types tested in their study. 

3D Culture Screenings

Previous research has shown that testing physiological drug response on cell cultures grown in 3D environments offers a significant advantage over 2D cell cultures. The researchers cite a paper providing strong evidence that there are measurable differences in cell proliferation, metabolic capacity, signaling behavior, and drug response in 3D versus 2D. This is an important concept that may help guide the efficacy of results in studies searching for new, effective therapeutic options to treat any disease in vivo.

Focusing on bladder cancer and using a 3D cell culture format, this team screened a total of 652 investigational therapeutics and 3 drug combinations in 17 bladder cancer cell lines.

MEK Inhibitors

MEK inhibitors have been proposed as a potential strategy for bladder cancers with high expression levels of KIF15, as KIF15 promotes bladder cancer cell proliferation by upregulating the MEK pathway. Through this study, the researchers found that the basal subtype of bladder cancer is significantly more sensitive to MEK inhibition than any other subtype. See Figure 4 below.

Figure 4: MEK inhibitor response correlates with basal subtype.
Figure 4: MEK inhibitor response correlates with basal subtype.

Conclusion

“As next steps, we pose that this work be used to further test additional therapeutic options for patients with bladder cancer. Moreover, this work highlights a need for biomarkers of drug response, beyond mutational data. Lastly, using these methods, we identify MEK inhibitors as a promising therapeutic in the basal bladder cancer subtype.”

Click here to read the full scientific paper, published in Oncotarget

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