The Precision Oncology Lab focuses on several research areas to provide translational improvements to clinical care for cancer patients.
Organoid-driven Precision Oncology
Patient-derived tumor organoids are miniaturized models of patient tumors that closely recapitulate the tumor heterogeneity, cancer mutations, genetic-epigenetic signatures and tumor microenvironment of the original tumor, including the immune components. The lab develops healthy and cancerous organoids obtained from patient biopsies and surgical samples and uses them to predict the therapeutic responses of patients. These organoids can be expanded in the laboratory, biobanked and genetically modified to create more complex disease models.
In the longer term, the lab aims to advance organoid technology by innovating next-generation tools of standardization, automation, and large-scale drug testing. One of these projects, funded by NIH, seeks to identify the epigenetic basis of therapeutic resistance in head and neck cancer. The lab is studying DNA-methylation patterns in various head and neck cancer subtypes to identify radiation and cisplatin resistance biomarkers.
Imaging innovation for clinical translation
The lab has a strong passion for innovative cancer imaging. Researchers work closely with the Molecular Imaging and Theranostics Center (MITC) for developing and testing new molecular imaging probes. Currently, the lab is developing strategies for imaging glutathione metabolism to predict radiation resistance in Keap1/Nrf2 muted tumors.
During postdoctoral research at Stanford Medicine’s Department of Radiation Oncology, Dr. Khan developed a method to image organoids and other in vitro models with PET radiotracers and compare them with patients' PET scans. This multi-model microscopy system, capable of co-imaging brightfield, fluorescence, bioluminescence and radioluminescence, provides a leading-edge platform for innovation in translational cancer imaging at the University of Missouri. The lab aims to apply this technology to advance precision oncology by discovering new imaging biomarkers of therapeutic resistance and, in particular, using patient-derived models.
Radiation biology of emerging radiation modalities
Radiation therapy and the principle of radiobiology is employed in more than 60% of all cancer treatments. The lab is currently interested in the radiobiology of two emerging modalities to help translate promising research to patient care.
FLASH Radiation Therapy
Using ultra-high doses of radiation delivered in less than a second, rather than using fractionation to space out doses, has shown signs of sparing healthy tissue while still killing tumor cells. By understanding the mechanism of tissue sparing by ultra-high dose rate (FLASH) radiation therapy, researchers can help translate this promising next-generation radiotherapy tool into clinical use. However, the lack of understanding of its radiobiology is a significant challenge. To this end, the lab studies radiation-induced DNA damage and repair pathways and how targeting antioxidant metabolism influences the FLASH effect.
Targeted Radionuclide Therapy
Targeted radionuclide therapy has shown promise to cure advanced metastatic disease. The radionuclides best suited for tumor therapy are those emitting ionizing radiation with short penetration into the tissue and releasing their energy in the proximity of their targets. In collaboration with University of Missouri Research Reactor (MURR) and MITC, the lab aims to study the radiobiology and cell-death pathways induced by emerging Alpha, Beta, and Auger radiopharmaceuticals.
