Researchers from the Science and Technologies Facilities Council’s (STFC) Central Laser Facility’s (CLF) Octopus Group have shown that a crucial interface in a lung cancer protein could offer a potential target for cancer treatments.
Published in Nature Communications, the findings could advance future research into more effective, long-lasting cancer therapies.
CLF scientists used advanced laser imaging techniques developed by STFC, Fluorophore Localisation Imaging with Photobleaching (FLImP), to obtain super-resolution images of a drug-resistant EGFR mutation known to contribute to cancer.
FLImP revealed structural details and, for the first time, showed how the molecules in the drug-resistant EGFR mutation interacted.
In addition to this, the Biomolecular and Pharmaceutical Modelling Group at the University of Geneva (UNIGE) provided additional analysis by using advanced computer simulations, combined with FLImP analysis, to provide atomistic details of the EGFR complexes.
“The simulations were able to push the effective resolution of the microscope beyond the limits of imagination,” almost touching the mutation site and seeing its effect, explained UNIGE’s Dr Yiannis Galdadas.
With this analysis, CLF researchers were able to compare the structural details of the mutated and healthy EGFR to determine interfaces between interacting molecules within the drug-resistant mutation critical for the growth of tumours.
Furthermore, additional mutations were introduced to the drug-resistant EGFR in cultured lung cells and in mouse models that interfered with the newly discovered interfaces.
As a result, the team found that one of the additional EGFR mutations could block cancer growth and further indicated that this mutation’s ability to promote cancer growth depended on these interfaces, which are hoped to potentially act as new targets for cancer therapies.
Professor Marisa Martin-Fernandez, leader of the CLF Octopus Group, commented: “If this interface proves to be an effective therapeutic target, it could provide an entirely new approach to much-needed pharmaceutical development.”
CLF is currently testing this research method on other EGFR mutations that are known to contribute to lung cancer with the aim of determining whether this interface plays a crucial role in the development of other cancers, including brain cancer.