Studying Cancer Stem Cells to Identify New Cancer Therapies
John Kuo, MD, PhD, has been interested in science and discovery nearly his whole life. It was when he became a physician-scientist that he also focused those interests on improving patient care. Kuo has been a neurosurgeon and brain cancer researcher with the UW Carbone Cancer Center since 2005.
“My research objective is to address clinical, patient-specific challenges,” Kuo said. “I study the biology of brain cancer in clinically relevant models in order to improve diagnostics and therapies for cancer patients.”
Kuo focuses much of his research on cancer stem cells. These stem cells are like cancer seeds: they are resistant to many treatments and can re-grow into the whole tumor. Some can also spread to other parts of the body, where just a few cells can grow into a metastatic cancer.
“Cancer stem cells may be why certain cancers, like glioblastoma, can’t be treated effectively and cured today,” Kuo said.
To study cancer stem cells, Kuo starts with patient-consented brain tumor tissue donated after surgery. His lab grows the samples under different conditions to select for growth of human cancer stem cells and cancer cells. Studying the molecular biology of these different cancer cell types that all originated from an individual patient’s cancer help Kuo and his colleagues to identify clinically-relevant biomarkers for prognosis and to inform possible therapies.
In one recent publication, Kuo and his colleagues identified an ion channel protein, hERG, that is abundantly expressed on the surfaces of some highly aggressive brain cancers. That same protein is also the target of FDA-approved drugs commonly used to treat depression or seizure. The researchers looked retrospectively at the survival of brain cancer patients who were already taking anti-hERG drugs.
“Those patients whose tumors expressed high levels of the hERG biomarker and also incidentally got anti-hERG drugs experienced better survival, whereas no benefit was observed for patients with low hERG-expressing tumors,” Kuo said. “That’s the power of patient-specific samples: the biology has clinical relevance, and this is how precision medicine aims to individualize therapies for patients.”
Kuo has a research group of about ten people, but he emphasizes that their research efforts are amplified with their collaborators throughout the UW campus. As a neurosurgeon-scientist, he provides the clinical and translational expertise to his basic science research collaborators.
One of those collaborators is UW Carbone Cancer Center member and radiology professor Jamey Weichert, PhD. Weichert has developed a small cancer-targeting molecule, called APC. Healthy cells quickly metabolize and eliminate APC, but cancer cells retain it over weeks. APC targets nearly all types of cancers tested, including brain cancers. It targets cancer stem cells, too.
“We can tag functions onto APC, such as a fluorescence label, so that surgeons could visualize and discriminate cancer cells from normal tissue during surgery,” Kuo said. “Or we can tag a drug to APC so that all cells within a patient’s cancer, even the resistant cancer stem cell population, are targeted for therapy.”
Kuo also collaborates with UW Carbone Cancer Center members Paul Sondel, MD, PhD and Zachary Morris, MD, PhD, on new immunotherapy approaches to target metastatic cancers. And he works with Carbone Cancer Center member and biomedical engineering professor Eric Shusta, PhD, to study the human blood-brain barrier with stem cell models. Together, they seek to improve drug delivery to the brain and spinal cord, which are difficult to access.
Ultimately, Kuo hopes his work will lead to more effective, personalized therapies for brain cancer patients.
“We want our work to get back to individual patients, because each patient’s cancer is different and changing genetically over time due to treatments,” Kuo said. “If we can make discoveries that improve an individual patient’s therapy and clinical outcome in real time, that would be terrific.”
Navigating Brain Tumor Care Workshop: May 6
The UW Carbone Cancer Center is holding its annual Navigating Brain Tumor Care Workshop on Saturday, May 6 from 8am to noon in the Health Sciences Learning Center. The workshop provides empowering information to people living with or affected by brain tumors. The event is free and open to the public. Register online
Date Published: 04/05/2017