Dr Olivier Pardo
I obtained my PhD in Biochemistry and Molecular Biology from Imperial College, after which I joined the CRUK London Research Institute for a post-doctoral position in the lab of Prof Julian Downward. I then came back to Imperial College to lead a research lab that focusses on understanding the mechanisms of drug resistance and metastasis in cancer. While we historically mainly worked on lung cancer, we more recently diversified and started similar research into breast cancer, choriocarcinoma and sarcoma.
Our work involves a wide collaborative network in the UK and internationally. This CRUK PhD studentship project is based on initial work performed in collaboration with the Wuhan Institute of Physics and Mathematics (Chinese Academy of Sciences, Wuhan, China) and various Divisions across Imperial College such as Chemistry and Structural Biology. This work proposed the kinase RSK4 as a novel and promising therapeutic target in lung cancer, the principal cancer killer worldwide and a disease in urgent need of novel therapies.
What is this project about?
We found that targeting RSK4 prevented in vitro lung cancer cells drug resistance and invasion, the two main reasons for failing to cure patients with this disease. Our Chemistry partners at Imperial College developed a series of novel inhibitors that prevent RSK4 activation and part of our CRUK-funded project is to test these in vivo to assess whether they may have potential for clinical use.
An important step in bringing new therapies to the clinic is understanding what patient population may better benefit from the new treatment. So, to define a particular subtype of lung cancer where this therapy is more likely to be efficient, we will also study what particular genetic background predicts positive response to RSK4 inhibition. For this, we are screening a large number of lung cancer cell lines and correlating response to RSK4 inhibition with the particular lung cancer genetic make-up of these cells.
In the long-term, this research will enable us to develop new drugs for lung and potentially other cancers. Indeed, we are now expanding our investigation to the role of RSK4 in other cancer types, such as breast, bladder, prostate and colon cancer.
Translating our basic research into patients’ benefit will require continued collaborations with the pharmaceutical industry to further develop these molecules and test them in clinical trials. The latter will be facilitated by the head of our lung cancer section, Prof Michael J Seckl, a clinician who has previously used findings from my lab to initiate several clinical trials in lung and other cancers.
How does this project align with the rest of our research?
RSK4 is only one of the potential therapeutic targets that my lab is currently working on. Indeed, we have recently published a number of papers demonstrating the role of several other kinases in cancer drug resistance or metastasis, such as FGFRs, S6K2 and MARK4. We are currently involved in developing inhibitors for these proteins or using existing agents to target them in the clinic (ie the currently running RADICAL clinical trial of an FGFR inhibitor in breast cancer). As a single target is unlikely to be useable in all types of cancers, working in parallel on these different candidates maximises our chances of finding appropriate therapeutic strategies for different malignancies.