OHSU

Research Story – Individualized Tumor Treatment

Changing the Face of Cancer

Unlocking the secrets of GIST tumors

Michael Heinrich, M.D.

I study gastrointestinal stromal tumors (GIST), a cancer that affects the digestive system. The main treatment for GIST is Gleevec (imatinib), a drug developed by Dr. Brian Druker, director of the OHSU Knight Cancer Institute, for patients with chronic myeloid leukemia. I helped determine that Gleevec could also treat patients with GIST.

Most GIST tumors contain certain mutant enzymes, and Gleevec fights those enzymes. Although this drug works well for many patients, some tumors are Gleevec-resistant. Our research found that Gleevec-resistant tumors had new gene mutations that prevented the drug from working as well. To kill these tumors, we helped develop Sutent (sunitinib). It targets the same enzymes as Gleevec and can also block the development of blood vessels in tumors.

What this means is that we can begin to develop an individualized approach to the treatment of GIST. We can tailor treatment based on the genetic make-up of the tumor.

In GIST, one of the mutant enzymes acts like a car motor that is stuck at full speed. Gleevec is the key to turn the motor off. But over time, GIST cells mutate (change), so Gleevec can't turn off the motor. Sutent is a different key that works on some Gleevec-resistant tumors but not all of them, depending on whether the key fits correctly or not..

We still need other types of keys (other drugs), to attack all of the possible resistance mutations. We need more studies to confirm these results and develop faster ways to test for these gene mutations. That’s why your support of our research at the OHSU Knight Cancer Institute is so important – it saves lives by helping us develop new treatments.

For more information, about our findings, read our two articles in the Journal of Clinical Oncology.