Adaptive therapy in non-muscle invasive bladder cancer

Team Red, 8th Annual IMO Workshop
Moffitt Cancer Center and Research Institute, Tampa, FL, USA


My team consisted of Philipp Altrock, Mik Black, Rafael Bravo, Oana Deac, Meghan Ferrall-Fairbanks, Gregory Kimmel, Roger Li, Karen Mann, Pierre Martinez, Margaret Myers, Fereshteh Nazari, Ana Osojnik, Hemachander Subramanian, Yannick Viossat, Michelle Wang, and Freddie Whiting.

BioRxiv Channel

We’ll have a report summarizing our findings at

Event Description

November 2nd the 8th Annual IMO Workshop concluded 4.5 days of intense collaborative research and problem-solving about evolutionary therapy. As in prior years, the workshop was comprised of both an educational event and competition during which the participants were divided into multiple teams combining clinical, experimental and theoretical members. This year 84 people participated, with 50 external visitors and 34 internal participants.

Team Green: (1st Place) Emma Carrick Smith, Gustavo De Leon, Mina Dinh, Khalid Hamed, David Lewis, Hui Ren, Christina Richards, Katerina Stankova, Holly Swain Ewald, Mathew Wicker, Joel Brown, Christine Chung, Audrey Freischel, Chandler Gatenbee, Arig Ibrahim Hashim, Mariyah Pressley, & Jeffrey West.

Team Orange: (2nd Place) Matthew Foster, Calum Gabbutt, Ester Gil Vazquez, Michalina Janiszewska, Adarsh Kumbhari, Ryan Schenck, Robyn Shuttleworth, Javier Urcuyo, Luis Zapata, Stanislav Avdieiev, Medhi Damaghi, Zeynep Eroglu, Jill Gallaher, Eunjung Kim, Kimberly Luddy, Tran Nguyen, & Mark Robertson-Tessi.

Team Blue: Xinzeng Feng, Jakob Nikolas, Dawn Lemanne, Cliona O’Farrelly, Immaculada Sorribes, Roisin Stephens, Maximilian Strobl, Iman Tavassoly, Noemi Vitos, Amrita Basu, Renee Brady, Chunzhe Duan, Heiko Enderling, Pedro Enriquez, Brandon Manley, Niveditha Nerlakanti, & Katarzyna Rejniak.

Team Yellow: Noemi Andor, Ou Deng, Nima Ghaderi, David Robert Grimes, Timon Heide, Xiaoming Liu, Jeffrey Peacock, Julia Pelesko, Ana Victoria Ponce Bobadilla, Seyedehsareh Seyedi, Jiawei Zhou, David Basanta, Bina Desai, Andriy Marusyk, Anna Miller, Robert Vander Velde, & Xiaohong Zhao.

Team Red: Mik Black, Rafael Bravo, Oana Deac, Pierre Martinez, Margaret Myers, Fereshteh Nazari, Ana Osojnik, Hemachander Subramanian, Yannick Viossat, Michelle Wang, Freddie Whiting, Philipp Altrock, Meghan Ferrall-Fairbanks, Gregory Kimmel, Roger Li, & Karen Mann.

As always the teams are presented with a cancer specific problem and then expected to come up with a model, solve it and give a presentation within the 4.5 days.

Event Details

Despite major advances in cancer therapies, most metastatic cancers remain fatal because tumor cells have a remarkable capacity to evolve drug resistance, both through genetic and non-genetic mechanisms. A common maxim in cancer treatment is to “hit hard and fast” through dose-dense strategies that administer the highest possible drug dose in the shortest possible time period. The maximum tolerated dose (MTD) principle has been the standard-of-care for cancer treatment, however, it has not resulted in consistent cures in patients with disseminated cancers. An evolutionary flaw in this MTD strategy is the assumption that resistant populations are not present prior to therapy. It is now clear that cancer cells can be insensitive even to treatments that they have never encountered before. Therefore, MTD therapy that is designed to kill as many cancer cells as possible, although intuitively appealing, may be evolutionarily unwise. When high doses of drug are applied continuously, competitive release allows rapid emergence of resistant populations because of the combination of intense selection pressure and elimination of all potential “sensitive” competitors. An approach we have pioneered at Moffit is to deliver the minimum effective dose (MED) by only treating a subset of the tumor, ensuring that a drug-sensitive population is left behind when treatment stops, and allowing it to reestablish. Then, through repeated cycles of treatment, the tumor is kept under control for extended periods of time. The timing of each treatment will be specific to each cancer patient; how they respond to the initial treatment will dictate when the current treatment should stop and when the next round should begin. We have termed this approach “adaptive therapy”, where the dose and timing are adapted to each individual patient’s cancer. Adaptive therapy is a subset of a larger class of evolutionary-enlightened therapeutic approaches that embrace evolutionary principles to try and stay one step ahead of the complex evolving system that is cancer.

While all participants find the event enriching and educational, the leaders of the winning teamof the event will be offered a $50K pilot grant to pursue their project further. This year Team Green, under the leadership of Joel Brown, was selected as the first place winners and the reciepents of the $50K pilot grant for their project entitled, “Designing and evaluating evolutionary therapies for advanced progressive thyroid cancer”

Congratulations, to Team Green and all the participants! We can’t wait to see what happens next year!