Sunday, August 27, 2017

A return to blogging and two new papers: Experimental measurement of evolutionary games and Evolutionary instability in collateral sensitivity networks

Well, the last year has been hectic. I moved my clinical practice to Cleveland Clinic, wrote and defended my thesis (corrections pending...) and have started to grow a research group here in the department of Translational Hematology and Oncology Research. I will begin asking each of the new group members to introduce themselves with short posts here soon, and hope to have at least bi-weekly update posts starting next month.

Before then however, I'm excited to highlight that the two posters that I highlighted on this blog just as I moved, are now full manuscripts. The first, led by +Andrew Dhawan studies how drug sensitivities change over the course of treatment, and even during drug holidays.

This work, which appeared in Scientific Reports, has gotten some attention and we were asked to write a more clinical follow on for Oncology Times called "Evading therapeutic resistance through collateral sensitivities: a paradigm shift?", which you can read here.

The most exciting result from this work was the idea that we need to think about collateral sensitivities a bit harder before we translate them directly to the clinic as they are dynamic even on very short timescales. The full paper, "Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer" can be read here:

A tantalizing piece of info here too was the not only did drug sensitivity change over the course of treatment, but so did radiation sensitivity...  More on this later.

The second project, an experimental method to directly measure the evolutionary games cancer cells play during the evolution of resistance has just yielded a new pre-print from the group, led by +Artem Kaznatcheev . Readers of this blog and #mathonco work in general will know that we've been working on evolutionary game theory and cancer for some time - really work started by +David Basanta. David and +Alexander Anderson and +Artem Kaznatcheev and I have now published something like 10 total papers between us on cancer and game theory ranging from studying how hormone therapy timing should work in prostate cancer to how we should think about how our drug scheduling affects tumor composition  and even more abstract ideas like how local cell topology affects evolutionary stable states and dynamics.

Transforming the payoff matrix using the Ohtsuki-Nowak transform allows an understanding of how spatial organization (locally) might change the game... (See Intercace paper linked above)

At issue is that the payoff matrix, the heart of evolutionary games, is usually invented rather than parameterized in any meaningful way. And even when it is it is done indirectly (from literature, or disparate measurements...).  To address this, +Artem Kaznatcheev came up with a clever experimental method to directly measure these games, and we found that the qualitative nature of the game itself can be changed!

So, if this piques your interest, wander over to the bioRxiv and check out the pre-print. With any luck it will be appearing soon in the pages of your favorite journal.

Here you can find "Cancer associated fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays"

OK, see you soon!  Happy reading.