Jacob Scott, MD, DPhil

Taussig Cancer Institute

ALL CANCER TYPES

Impact Award

Exploiting the weaknesses a tumor exposed during the evolution of drug resistance in Ewings Sarcoma

Ewings Sarcoma is a rare but deadly form of bone cancer that primarily afflicts children. While it can be cured with a combination of surgery or radiation and chemotherapy, it often recurs and then chemotherapies that we use stop being effective. This process, where these cancers evolve resistance to our best drugs, is the same process that occurs in many cancers, and is one driven by through a series of mutations in the DNA of a tumor.

Promisingly, the changes that result in drug resistance often also result in weaknesses. When the tumors get good at one thing (resisting our first therapies), they often expose vulnerabilities to others. And, even though these changes seem random, we have begun to find patterns in them: patterns which will allow us to stay one step ahead of the tumors and take advantage of these vulnerabilities.

So, instead of waiting for resistance to develop, we plan to use our VeloSano Impact Award to perform many, many of individual evolution experiments using a programmable robotic system. Instead of expecting the same thing to happen each time we do the experiment — we expect an ensemble of different results: a predictable ensemble. Once we develop the ability to predict these vulnerabilities, we hope to use this information to inform second line therapies for those Ewings Sarcoma patients whom our first line chemotherapies have failed.

IN OTHER WORDS

By predicting how Ewings Sarcoma evolves resistance to our best drugs, and how this evolution exposes vulnerabilities in the tumors, we are working to identify second line therapies for patients whom our first line drugs have failed.