Using lasers to develop fluorescent anti-cancer drugs
Evotec has teamed up with the Harwell Imaging Partnership (HIP) to maximise the potential of their research into cancer treatment drugs using the Science and Technology Facilities Council (STFC)’s Central Laser Facility (CLF).
Some drug-based cancer treatments work by inhibiting the signals that cause mutated cancer cells to divide and multiply, but the efficiency of these drugs varies greatly. Treatments are often effective for a short while, but the disease can return because signals, initially blocked by the drugs, start finding alternative routes to multiply mutated cells. A better understanding of this biological process is critical for scientists wishing to refine the design of inhibitor drugs and improve predictions of therapeutic outcomes.
To track the effectiveness of the drugs, Evotec need to image them in cells at the molecular level. This requires the use of a fluorescing component that glows under laser illumination.
The HIP and the Bio-Med Network funded a PhD studentship with Evotec to support the synthesis of fluorescent derivatives of tyrosine kinase drugs, specifically Gefitinib. The collaboration brings together the world-leading cancer expertise of King’s College London, the comprehensive drug discovery skills of Evotec and a unique repertoire of cross-disciplinary advanced imaging methods provided by the OCTOPUS cluster of lasers at STFC’s CLF. This allows researchers to adopt a combination of techniques on sample drugs.
With the facilities and expertise accessed through the HIP, Evotec are working together with the CLF on the development of a series of fluorescent cancer cell inhibitors that would enable them to deploy assays to characterise how inhibitor molecules interact with their receptor targets in cells. This could ultimately be used to study the effectiveness of the anti-cancer drug in the clinic.
Using these techniques, the partnership between the CLF and Evotec has tested the potential of a fluorescence derivative of cancer drug Gefitinib to characterise the signalling activity of groups of key cancer-related receptor mutants in five cell lines. This could provide a greater understanding of the mechanisms leading to the development of drug resistance, and may help scientists perceive new ways of preventing patients from becoming unresponsive to the treatment.
The ability to conduct single-cell imaging of inhibitor drugs binding their target in cancer cells is a critical step towards developing novel anti-cancer drugs. It is believed that this work will contribute to the eventual development of patient-by-patient cancer treatment options.
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