Oluwaseun O. Akinduro, MD, Chief Resident Physician, Department of Neurological Surgery at the Mayo Clinic in Jacksonville, FL, received the 2021-22 NREF & AANS/CNS Section on Tumors Research Fellowship Grant for his project “Targeting Chordoma Therapy Resistance Through the YAP Pathway.”
An article based on his research will be the April 2023 cover story in JNS Spine.
Dr. Akinduro gave NREF the following update on his research: The primary goal of my research is to develop targeted therapies for primary and secondary spine cancers. Chordoma is the most common primary malignant cancer of the spinal column while metastasis is the most common tumor of the spinal column overall, so these tumors were my primary focus. For this project we utilized microparticles loaded with a drug called verteporfin to treat chordoma and spinal metastatic cancer.
Verteporfin targets the yes-associated protein (YAP) pathway which is highly expressed in many cancers including the ones we studied. I was also able to use these microparticles to make chordoma and spinal metastasis more sensitive to radiation therapy. From a mechanistic perspective, I was able to gain a newfound understanding of how tumors like chordoma can resist radiation damage, and this knowledge can be applied to any tumor type. By targeting unique genetic drivers of metastasis with verteporfin-loaded microparticles in vitro and in vivo, we demonstrated that inhibition of the YAP regulatory axis leads to diminished metastatic invasion properties and enhanced radiotherapy effectiveness in primary and secondary spine cancer cells, laying the groundwork for future novel targeted therapy.
“Receiving the NREF grant solidified my desire and confidence to become a neurosurgeon-scientist. I received this grant at the perfect time, and I honestly may have decided to stick with a career in clinical work only if it weren’t for my year in the lab funded by the NREF.”
