Here I am back at the Crick, on my orderly desk, next to my chaotic lab bench with hundreds of slides to be scanned, contemplating the ideal approach to write about my experience as a researcher. After days, finally, I have decided that similarly to my surroundings, it should be balanced, not bleak but neither deluded. I shall avoid misleading motivational quotes and exaggerations and attempt to paint a realistic picture of my personal experience.
My master’s research project studying cancer evolution was my first exposure to a lab. No large colourful mixtures present, no floating laser keyboards, none of these misrepresentations. A lot of busy offices, benches and unknown machines used by curious people with different backgrounds. The imposter syndrome kicked in immediately, which is common when introduced to an unfamiliar world. On the other hand, I was excited to explore and learn as many techniques as possible, to be thoroughly equipped to pursue a PhD degree.
Panos Anastasiou with Julian Downward at the BACR 60 Anniversary Meeting in Nottingham, June 2022
I did manage to learn a few techniques; however, I now also find valuable characteristics adopted from my mentors and peers. Supportive supervisors and colleagues, with their own struggles and successes, were essential to forming a pragmatic idea of what real research entails. Guiding me, devoting many of their valuable hours to teach me more than a couple of techniques; how to design an experiment, how to apply for a studentship, how to write a scientific report etc., each one with a different aspect to analyse and assimilate. One aspect that confusingly fascinated me was the persistence of constantly trying new experiments and failing, and then again back to it. It requires exceptional persistence to brush off the fact that you spent time and effort to just get a negative result. Afterall, the aim is to formulate ways to treat a group of diseases that are constantly evolving and eventually adapting to our efforts.
Failing and succeeding through persistence is a familiar pattern to all levels of research, especially cancer. Exemplar is the story of Kras, a protein acting as a hub of mitogenic and survival signalling and a frequent oncogenic driver of lethal solid cancers. Since its discovery in 1982, many efforts to target Kras had failed and therefore, it was referred to as “undruggable”. I still remember one of my lecturers’ remark during my Master’s, “the person that figures this out, definitely a Nobel prize’. Ironically, two years before that, 2013, Kevan Shokat had published a paper where they had developed a molecule which could bind and inhibit KrasG12C, a mutant form of Kras present in many cancers. Kras was no more “undruggable”. Fast-forward 8 years, the first Kras inhibitor was approved for KrasG12C-mutant lung cancer patients. This was only the beginning as companies and labs have already announced the successful development of inhibitors that target other mutant forms of Kras.
Why is this important to my personal experience? Because the persistence and ingenuity of others have enabled me to use newer generations of those inhibitors to study Kras and carry out my PhD project. As with all science stories, they are never-ending; it turns out tumours through several mechanisms develop resistance to these inhibitors. My aim is to combine Kras inhibitors with other novel therapies to prevent development of resistance and harness the immune system to treat and if possible, ultimately cure lung cancer. This involves daily treatments of lung cancer-bearing mice and investigating the effects of these inhibitors on the tumour microenvironment. A project that could lead to the design of new clinical trials and treatment options for patients.
Panos Anastasiou receiving The BACR Hamilton Fairley Prize from Julian Downward at the BACR 60 Anniversary Meeting in Nottingham, June 2022
Although self-emanating persistence is useful, from time to time a “nudge” from your surroundings can have an equally significant impact. This June I had the opportunity to attend the 60th Anniversary BACR conference in Nottingham, my first ever science conference! It was intimidating at first, considering that I also had to present my PhD research project in a poster. However, with the support of people from my lab, my experience of the conference was incredible. I got introduced to people, fellow scientists from all over the world, even supervisors of other labs, where I had wonderful conversations and exchange of ideas. Fellow PhD students came and introduced themselves making it even more comfortable and enjoyable as we started sharing experiences. Everyone with a distinct angle to solve a hypothesis; it was the highlight of the conference. The talks, equally fascinating, kept me engaged throughout from Antony Letai’s talk of using BH3 mimetics to sensitise cancer cells to NK cell-mediated killing to the keynote speaker…Kevan Shokat’s talk of successfully targeting KrasG12S, another mutant Kras! My experience of the conference was completed with a poster prize, an achievement reinforcing my motivation to continue doing my project persistently.
After a few readthroughs of this blog I feel something is missing, a big closing. This is my perspective of research, always unfinished business. Unanswered questions, leading to a build-up of anticipated excitement when I get the next positive result, a finished experiment, a complete project, constantly surrounded with guidance from my peers and mentors.
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