It was the final year of my PhD, and I was presenting a poster at a conference, alongside my supervisor Dr Kathy Gately. We were showing off our new panel of PI3K inhibitor resistant lung cancer cell lines, which we had developed and begun to characterize. We were excited to tease out which signalling pathways might be playing a role in resistance to these drugs.
Along came Dr Michael O’Neill, the co-founder of Inflection Bioscience, who had recently licenced a drug that targeted the PIM kinases. At the time, I had never heard of PIM. He saw our poster, and suggested we should test their drug in our cell lines. It seemed straight forward enough.
After a couple of quick ‘look see’ experiments, we ended up submitting a grant.
Then some student projects.
Before we knew it, this ‘quick win’ was becoming a driving interest for Kathy, and she was gathering researchers along the way (notably Dr Gillian Moore). I had left Kathy’s lab at this stage, but as a wider team we were beginning to build up a picture of how best we could potentially develop these drugs in the lung cancer space.
PIM research didn’t stop for Kathy, and it didn’t stop for me either.
When interviewing for a postdoc position in University College London with Dr Hayley Whitaker, I was asked ‘if you had access to human prostate cancer specimens, what would you do with them?’ On a whim, and with interview pressure weighing down on me, I responded ‘well there’s this really exciting drug target called PIM in lung cancer, I think it looks like it might be promising in prostate cancer too, so I’d probably run some experiments on that’.
I arrived home to Dublin that night, exhausted after a long day of travel & interviewing, and found out immediately that I’d been invited to a second round interview. This was great – but it would be in London again, in just a few days! I purchased a second pair of flights, cried over my bank balance for a moment, and then hunkered down in our basement office for the weekend, trying to pull together a presentation that had been assigned for the second round. The challenge that had been set was of course ‘if you had access to human prostate cancer specimens, what would you do with them?’ How could I present on anything other than PIM after suggesting it in my previous interview?!
I rushed a project pitch, which by chance turned out quite promising. There were a good few papers looking at PIM in prostate cancer, but not many looking at drug treatments, and none looking at the same co-targets that we were working on in lung cancer. I checked with Kathy if it was ok with her for me to present this, while rushing out of the building to get to the airport – but our conversation got slightly side-tracked when she told me she was expecting a baby! Safe to say PIM got a bit overlooked that lovely day.
The presentation went well, I got the job, and to my delight I was offered the chance to actually work on the project that I had pitched in the interview. What a wonderful opportunity for a postdoc to be given that level of freedom!
In order to differentiate my new prostate cancer project from the work Kathy was leading on, I set out to investigate a wider panel of drugs, including the PIM inhibitors but also quite a few others. The aim was to test promising late stage pre-clinical drugs in human prostate cancer tissue, using ex vivo culture and new omics technologies. I gathered some preliminary data and submitted it as a fellowship proposal, trying to position myself as someone who worked on drug development in general. Thankfully, I was successful.
It wasn’t mean to be a ‘PIM project’. But as luck would have it, PIM wasn’t going away.
One by one, the other drugs dropped off for one reason or another. Some couldn’t be investigated in an ex vivo model because they needed to be metabolised within the body, some needed to build up for a few weeks before an effect would be seen, some failed during concurrent animal testing, and some just showed disappointingly little activity in my model. By the time the work was close to publication, we were down to just 4 different treatments, and they were a very similar panel to what Kathy was leading on in lung cancer. I hope she forgives me!
Now, years later, we’ve just had our first original article come out on PIM in prostate cancer1. This is our first ‘flag in the sand’ where we put forward the idea of co-targeting PIM with the PI3K pathway. There are bigger and more detailed works to come from this in the future. If you’d like to read about the paper itself, I wrote a tweetorial that you can read unfurled here: https://threadreaderapp.com/thread/1300721602854871040
This paper came off the back of a couple of reviews on PIM as a drug target3,4, and there is of course more on the way.
Now, plans are brewing for wider PIM collaborations, and who knows, maybe PIM will stick around in my world even longer.
Did I ever set out to become a PIM researcher? No, not particularly.
But I suppose the lessons learned here are to say yes to opportunities, and to follow the data – if something isn’t your ‘plan A’ but it might make a difference to cancer patients in the future, then why wouldn’t you follow it?
Extra credit to my friend AJ (@AyoksAJ) for his very inspiring ‘Say Yes’ presentation to our postdoc networking group a few years ago, which still sticks around in my mind, and lead me to say YES to an opportunity that came my way this morning – let’s see where this one goes!
Thank you to Kathy, and to all the PIM friends I’ve made over the years.