Targeting microtubules to overcome resistance to chemotherapy drugs

With very few treatment options for ovarian cancer, many women become resistant to one of the two key drugs used in chemotherapy, and sadly have no other alternatives. Professor Ahmed's team looked at how microtubules are involved in resistance to paclitaxel chemotherapy.

With very few treatment options for ovarian cancer, many women become resistant to one of the two key drugs used in chemotherapy, and sadly have no other alternatives. Overcoming this resistance to chemotherapy is a major challenge and a key priority in Target Ovarian Cancer’s research strategy.

It has been shown previously that microtubules, which act like scaffolding within a cell, can influence how tumour cells respond to paclitaxel chemotherapy. Professor Ahmed's team looked at how microtubules are involved in resistance to paclitaxel. Their goal was to improve the effectiveness of paclitaxel by including other drugs that make cancer cells more susceptible to damage done by this type of chemotherapy.

The team has shown, using cell lines in the laboratory, how an enzyme called FER regulates the stability of microtubules in ovarian cancer cells. They have also shown that tumour cells can become more sensitive to paclitaxel when FER is prevented from working properly, by removing it or targeting it with a specific small molecule. These results are an important achievement, which could be translated to patients to develop more effective therapies.

Fact file 

Researcher: Professor Ahmed Ahmed
Institution: University of Oxford 
Project dates: January 2013 to November 2016 
Funding awarded: £178,000 
Project status: complete 
Key publications: Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, et al (2018) Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation, Nature Communications, 2018; 9(1):476, DOI: https://doi.org/10.1038/s41467-017-02811-7

Photograph of Professor Ahmed Ahmed
These results provide strong evidence that by targeting FER we can improve the effectiveness of paclitaxel in killing tumour cells. The small molecules that target FER could potentially be developed into new drugs for ovarian cancer, to enhance the effectiveness of paclitaxel treatment.
Professor Ahmed