Profesionales médicos

Feb. 26, 2025

Mayo Clinic neurosurgeons are investigating new approaches for the treatment of chordoma. A locally aggressive cancer, chordoma is challenging to resect, highly recurrent, and resistant to radiation and chemotherapies.

"Optimal resection requires a neurosurgeon with specialized training in primary spinal tumors," says Oluwaseun O. Akinduro, M.D., a neurosurgeon at Mayo Clinic in Jacksonville, Florida. "At Mayo Clinic, we also are seeing promising results from early studies focused on making these tumors less resistant to radiation therapy."

As a tertiary center, Mayo Clinic has experience and expertise with this understudied disease. A multidisciplinary team provides personalized treatment at all three Mayo Clinic main campuses. Early referral is recommended.

"Physicians who see very bright spots anywhere in the clivus, spine or sacrum on T2-weighted MRI should suspect chordoma," Dr. Akinduro says. "The best bet is to refer the patient to us prior to biopsy because the biopsy needs to be done in a way that won't interfere with future tumor resection."

Expert care and cutting-edge research

Gold standard treatment for chordoma is en bloc resection with wide tumor margins. "The tumor might involve an entire spinal level or even two spinal levels. But we have to work around the entirety of the tumor and remove it in one piece," Dr. Akinduro says. "It's a time-consuming, complex surgery."

Another complicating factor is chordoma's midline growth pattern, which causes tumors to invade critical neural, vascular and bone structures. Mayo Clinic's multispecialty approach means that vascular, thoracic and plastic surgeons can assist as needed. Expert oncologists and radiation oncologists are also an integral part of the team.

"Chordoma is a very challenging tumor that needs multidisciplinary care," Dr. Akinduro says. "All of our experts come together and focus on patient outcomes."

If tumor-free margins can't be obtained, surgery is followed by high-dose proton-based radiation therapy. A Mayo Clinic study published in Neurosurgical Focus found that patients receiving proton-based therapy had a 40% likelihood of tumor recurrence, compared with an 88% chance of recurrence for patients who received standard photon radiation therapy.

Efforts to further improve radiation therapy focus on yes-associated protein (YAP), which regulates gene transcription and cell proliferation. Researchers in Dr. Akinduro's spinal oncology laboratory have found that verteporfin — a medication approved by the Food and Drug Administration — is a potent YAP inhibitor in xenograft laboratory models. The work is described in a preprint manuscript in bioRxiv.

"Verteporfin renders chordoma more sensitive to radiation via inhibition of the DNA damage repair cascade," Dr. Akinduro says. "The drug also promotes accumulation of cells at the G2-M checkpoint, when they are most susceptible to radiation damage," Dr. Akinduro says.

Verteporfin has a short half-life. Mayo Clinic researchers use a novel microparticle to deliver the drug to laboratory models. That facilitates sustained release of the drug over time, prolonging exposure to it.

"Chordoma tumors cells appear to be most susceptible to radiation damage when they are at the G2-M checkpoint. But since chordomas are slow-growing, the probability that any tumor cell will be in G2-M at any given time is low," Dr. Akinduro says. "Prolonging the therapeutic concentration of verteporfin might increase the fraction of tumor cells in G2-M and thus enhance radiosensitivity. We are still investigating this further and confirming these results, but the preliminary results are very encouraging. Our ultimate goal is to one day use these microparticle in patients to make the tumors more sensitive to radiation."

The synergy of clinical care and research fuels Mayo Clinic's efforts to improve patient care. "As an academic institution, we are focused on patient outcomes but also able to combine that with translational research," Dr. Akinduro says.

For more information

Ghaith AK, et al. Proton versus photon adjuvant radiotherapy: A multicenter comparative evaluation of recurrence following spinal chordoma resection. Neurosurgical Focus. 2024;56:e9.

Akinduro OO, et al. Inhibition of yes-associated protein (YAP) with verteporfin enhances radiosensitivity in chordoma by inducing G2M arrest and inhibiting the DNA damage response. BioRxiv. Preprint.

Refer a patient to Mayo Clinic.