Rudy A Menon PhD Studentship: Spring/Summer 2025

The following is written by Rita Pereira, the second Rudy A Menon Foundation funded PhD student working at the ICR.

In my last report, I mentioned that one of my big achievements was the fact that I was able to establish several EGFR-altered patient-derived cell lines and one subsequent in vivo model in which these cells form tumours in mice. I have now been able to build on that and have been able to gather eight EGFR-altered patient-derived cell lines, of which five generated in vivo models that we can use for drug testing.

Despite being a great resource, patient-derived in vivo models have certain issues to overcome, including the fact that they do not have a full immune system, which can lead to different drug responses. To overcome this I am attempting to generate a genetic model of these tumours directly in mice with a full immune system, allowing for the testing of different treatment options. In order to do this, I have created what are called ‘plasmids’ of short DNA sequences containing mutations in genes we believe will cause tumours. I will introduce these into mice using an advanced technique called in utero electroporation (IUE) - I have been fortunate to develop a working relationship with technicians at the Francis Crick Institute, who helped me complete all the relevant training. I have several IUE experiments currently ongoing and despite still being in early days, it seems that a number of them have been successful in generating tumours.

Another key aspect of my PhD that I was keen to advance was testing different types of EGFR inhibitors in the models I have been able to generate. I have to date screened 18 different drugs in eight of our models. This resulted in a range of different sensitivities that seem dependent on the cell line background and drug type. It is well known in the field that single agents as a form of therapy show limited efficacy in patients. Therefore, from this work, I have been able to select initially two inhibitors that showed promise to test in combination with our collection of over 800 different drugs. We have also established collaborations with colleagues in the US, who are sending us two new EGFR inhibitors that are showing promise in other tumour types. Over the next few months, I will work on testing these new EGFR compounds as well as the combinations in a smaller panel of patient-derived cells lines, followed by carefully confirming the results. This will hopefully put us a step closer to testing these inhibitors in vivo. I will also carry on with the IUE experiments and characterise any models generated via this technique. As the GC conference approaches, I will be working on putting these results together to present to our colleagues and hopefully get valued input on my project.

I am continually grateful for The Rudy A Menon Foundation’s support. I’m looking forward to this year’s Walk around the World and hope to see you soon for the Rudy walk.