Details

Autor(en) / Beteiligte

• Shankar, Ganesh M.
• Kirtane, Ameya R.
• Miller, Julie J.
• Mazdiyasni, Hormoz
• Rogner, Jaimie
• Tai, Tammy
• Williams, Erik A.
• Higuchi, Fumi
• Juratli, Tareq A.
• Tateishi, Kensuke
• Koerner, Mara V. A.
• Tummala, Shilpa S.
• Fink, Alexandria L.
• Penson, Tristan
• Schmidt, Stephen P.
• Wojtkiewicz, Gregory R.
• Baig, Aymen
• Francis, Joshua M.
• Rinne, Mikael L.
• Batten, Julie M.
• Batchelor, Tracy T.
• Brastianos, Priscilla K.
• Curry, William T.
• Barker, Fred G.
• Jordan, Justin T.
• Iafrate, A. John
• Chi, Andrew S.
• Lennerz, Jochen K.
• Meyerson, Matthew
• Langer, Robert
• Wakimoto, Hiroaki
• Traverso, Giovanni
• Cahill, Daniel P.

Titel

Genotype-targeted local therapy of glioma

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2018-09, Vol.115 (36), p.E8388-E8394

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Aggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with lower-grade glioma. However, progression in many of these patients is characterized by local regrowth. Most lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations, which sensitize to metabolism-altering agents. To improve local control of IDH mutant gliomas while avoiding systemic toxicity associated with metabolic therapies, we developed a precision intraoperative treatment that couples a rapid multiplexed genotyping tool with a sustained release microparticle (MP) drug delivery system containing an IDH-directed nicotinamide phosphoribosyltransferase (NAMPT) inhibitor (GMX-1778). We validated our genetic diagnostic tool on clinically annotated tumor specimens. GMX-1778 MPs showed mutant IDH genotype-specific toxicity in vitro and in vivo, inducing regression of orthotopic IDH mutant glioma murine models. Our strategy enables immediate intraoperative genotyping and local application of a genotype-specific treatment in surgical scenarios where local tumor control is paramount and systemic toxicity is therapeutically limiting.