Newswise — Winner of the Mahaley Clinical Research Award, Ganesh Mani Shankar, MD, presented his research, Genotype-based, Local Targeted Therapy for Glioma, during the 2018 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting.

Aggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with lower-grade glioma. Lower-grade gliomas are often characterized by mutations in metabolism-related genes IDH1/2. While the initial therapeutic strategy is aggressive neurosurgical resection, this strategy may be limited by adjacent eloquent cortex resulting in local failures. Recent studies have demonstrated that IDH mutant cells are sensitive to metabolic therapeutics, but these are limited by systemic toxicities. To improve local control of IDH1 mutant gliomas and avoid systemic toxicity associated with metabolic therapies, the study authors developed a rapid diagnostic tool coupled with a sustained release microparticle drug delivery system containing an IDH1-directed NAMPT inhibitor.

To facilitate the intraoperative decision to apply targeted therapeutics, the authors developed an intraoperative diagnostic assay to identify glioma hotspot mutations in IDH, TERT promoter, H3F3A or BRAF within 30 minutes. Microparticles containing NAMPT inhibitors were designed to provide sustained local delivery of these compounds. Microparticles were tested for in vitro activity in cell culture and in vivo efficacy in murine orthotopic IDH1 wild-type and mutant glioma models.

Microparticles loaded with the NAMPT inhibitor, GMX-1778, potently decreased viability of IDH1 mutated cancer cells, but not in wild-type cells, in a time-dependent manner in vitro. In murine models, microparticles delivered intracerebral therapeutic concentrations of drug without detectable systemic toxicity. In mice with established orthotopic tumors, surgical implantation of microparticles did not affect tumor growth in an IDH1 wild-type glioma, while resulting in a significant decrease in tumor growth and prolonged survival in IDH1 mutant glioma.

This paradigm of genotype-directed local therapy introduces a novel workflow in surgical oncology that can be extended to other tumors characterized by targetable molecular alterations to improve local disease control at the surgical margin.

Author Block: Ameya Kirtane, PhD; Hiroaki Wakimoto, MD, PhD; Kensuke Tateishi, MD, PhD; Fumi Higuchi, MD, PhD; Tareq Juratli, MD; Matthew Meyerson, MD, PhD; Fred Barker, MD; A John Iafrate, MD, PhD; Robert Langer, PhD; Giovanni Traverso, MD, PhD; Daniel Cahill, MD, PhD

Disclosure: The author reported no conflicts of interest.

Media Representatives: The 2018 AANS Annual Scientific Meeting website’s press section will include releases on highlighted scientific research, AANS officers and award winners, Neurosurgery Awareness Month and other relevant information about the 2018 program. Releases will be posted on the 2018 AANS Annual Scientific Meeting website. If you have interest in a topic related to neurosurgery or would like to interview a neurosurgeon — either onsite or via telephone — during the event, please contact Alice Kelsey, AANS associate executive director, via email at [email protected].

About the 2018 AANS Annual Scientific Meeting: Attended by neurosurgeons, neurosurgical residents, medical students, neuroscience nurses, clinical specialists, physician assistants, allied health professionals and other medical professionals, the AANS Annual Scientific Meeting is the largest gathering of neurosurgeons in the nation, with an emphasis on the field’s latest research and technological advances. The scientific presentations accepted for the 2018 event will represent cutting-edge examples of the incredible developments taking place within the field of neurosurgery. Find additional information about the 2018 AANS Annual Scientific Meeting and the meeting program here.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 11,000 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. Fellows of the AANS are board-certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons of Canada or the Mexican Council of Neurological Surgery, A.C. Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the spinal column, spinal cord, brain, nervous system and peripheral nerves.

 

For more information, visit www.AANS.org.