November 9, 2016
by Artem Kaznatcheev
I am weathering the US election in Tampa, Florida. For this week, I am back at the Moffitt Cancer Center to participate in the 6th annual IMO Workshop. The 2016 theme is one of the biggest challenges to current cancer treatment: therapy resistance. All five teams participating this year are comfortable with the evolutionary view of cancer as a highly heterogeneous disease. And up to four of the teams are ready to embrace and refine a classic model of resistance. The classic model that supposes that:
- treatment changes the selective pressure on the treatment-naive tumour.
- This shifting pressure creates a proliferative or survival difference between sensitive cancer cells and either an existing or de novo mutant.
- The resistant cells then outcompete the sensitive cells and — if further interventions (like drug holidays or new drugs or dosage changes) are not pursued — take over the tumour: returning it to a state dangerous to the patient.
Clinically this process of response and relapse is usually characterised by a (usually rapid) decrease in tumour burden, a transient period of low tumour burden, and finally a quick return of the disease.
But what if your cancer isn’t very heterogeneous? What if there is no proliferative or survival differences introduced by therapy among the tumour cells? And what if you don’t see the U curve of tumour burden? But resistance still emerges. This year, that is the paradox facing team orange as we look at chronic myelomonocytic leukemia (CMML) and other myeloid neoplasms.
CMML is a leukemia that usually occurs in the elderly and is the most frequent myeloproliferative neoplasm (Vardiman et al., 2009). It has a median survival of 30 months, with death coming from progression to AML in 1/3rd of cases and cytopenias in the others. In 2011, the dual JAK1/JAK2 inhibitor ruxolitinib was approved for treatment of the related cancer of myelofibrosis based on its ability to releave the symptoms of the disease. Recently, it has also started to see use for CMML.
When treating these cancers with ruxolitinib, Eric Padron — our clinical leader alongside David Basanta and Andriy Marusyk — sees the drastic reduction and then relapse in symptoms (most notably fatigue and spleen size) but none of the microdynamical signs of the classic model of resistance. We see the global properties of resistance, but not the evidence of selection. To make sense of this, our team has to illuminate the mechanism of an undetected — dark — selection. Once we classify this microdynamical mechanism, we can hope to refine existing therapies or design new therapies to adapt to it.
Read more of this post
Hackathons and a brief history of mathematical oncology
October 28, 2017 by Artem Kaznatcheev 5 Comments
It was Friday — two in the morning. And I was busy fine-tuning a model in Mathematica and editing slides for our presentation. My team and I had been running on coffee and snacks all week. Most of us had met each other for the first time on Monday, got an inkling of the problem space we’d be working on, brainstormed, and hacked together a number of equations and a few chunks of code to prototype a solution. In seven hours, we would have to submit our presentation to the judges. Fifty thousand dollars in start-up funding was on the line.
A classic hackathon, except for one key difference: my team wasn’t just the usual mathematicians, programmers, computer & physical scientists. Some of the key members were biologists and clinicians specializing in blood cancers. And we weren’t prototyping a new app. We were trying to predict the risk of relapse for patients with chronic myeloid leukemia, who had stopped receiving imatinib. This was 2013 and I was at the 3rd annual integrated mathematical oncology workshop. It was one of my first exposures to using mathematical and computational tools to study cancer; the field of mathematical oncology.
As you can tell from other posts on TheEGG, I’ve continued thinking about and working on mathematical oncology. The workshops have also continued. The 7th annual IMO workshop — focused on stroma this year — is starting right now. If you’re not in Tampa then you can follow #MoffittIMO on twitter.
Since I’m not attending in person this year, I thought I’d provide a broad overview based on an article I wrote for Oxford Computer Science’s InSPIRED Research (see pg. 20-1 of this pdf for the original) and a paper by Helen Byrne (2010).
Read more of this post
Filed under Commentary, Reviews Tagged with conference, current events, IMO workshop, mathematical oncology