March 09, 2018
Researchers at The University of Kansas Cancer Center are studying tiny vesicles that may help lead to more targeted cancer therapies. Also called exosomes, these microvesicles act as “fingerprints” of a tumor’s identity, providing early clues to cancer cases.
“These exosomes are important because they are usually produced when a tumor is really small, less than one centimeter in size. Most imaging techniques are not able to detect a tumor that size,” Safi Atay, Ph.D., a senior research scientist in Andrew Godwin’s Lab, says.
Atay concentrates her research on a very rare type of sarcoma, GIST (gastrointestinal stromal tumor), and the exosomes it derives. There are about 4,000 to 6,000 GIST cases in the United States each year. These tumors can start anywhere in the GI tract, but they occur most often in the stomach or the small intestine.
A hallmark of GIST is the KIT receptor, which is found in about 80 percent of patients. The KIT oncogene drives tumor growth and proliferation. Therapies such as imatinib target and block this receptor to stop cancer growth.
“This therapy has done wonders for patients, but it can have uncomfortable side effects,” Atay says.
By better understanding the exosomes’ role in the development of cancer, Atay says there is an opportunity to create more targeted therapies. Her work, which was published in Molecular & Cellular Proteomics, provides new insights into GIST-derived exosomes, revealing potential diagnostic biomarkers.
Atay collaborated with Andrew Godwin, Ph.D., professor and director of molecular oncology and deputy director of The University of Kansas Cancer Center, Dr. Michael Merchant, associate professor at the University of Louisville, and Dr. Mohammad Milhem, a medical oncologist at the University of Iowa. She compared longitudinal samples derived from primary and metastatic GIST patients before, during, and after imatinib treatment.
After isolating and examining the exosomes in each sample, Atay noticed that the metastatic patients had a much higher level of circulating exosomes compared to non-metastatic patients. Furthermore, Atay found an additional biomarker, a vesicle protein, prevalent in the metastatic patient’s samples.
“With our longitudinal samples, you can watch the evolution of that protein. If it stops showing up in a patient sample, it means they are responding to the drug. If a patient expresses more of the protein, they are not responding. Not only did we find that particles in the blood can serve as an early indicator of metastatic progression, but this protein marker, when used in conjunction with KIT, can forecast a patient’s response to treatment.” Atay said.
With this information, clinicians may someday be able to tailor a patient’s treatment based on exosomes in their blood sample.
“Predicting how an individual will respond to therapy and then modifying their treatment accordingly is a step towards precision medicine,” Atay said. “Our findings carry that potential, and it’s exciting!”