AUTHOR=Ghanem Paola , Fatteh Maria , Kamson David Olayinka , Balan Archana , Chang Michael , Tao Jessica , Blakeley Jaishri ,  The Johns Hopkins Molecular Tumor Board Investigators , Canzoniero Jenna , Grossman Stuart A. , Marrone Kristen , Schreck Karisa C. , Anagnostou Valsamo , Pratilas Christine , Botsis Taxiarchis , Xian Rena , Gocke Chris , Ming-Lin Tseh , Halper-Stromberg Eitan , Zou Ying , Hardart Kent , Spiker Jonathan , Kreimeyer Kory , He Ting , Fiallos Katie , Petry Dana , Visvanathan Kala , Wolff Antonio , Santa-Maria Cesar , Nunez Raquel , Meyer Christian , Laterra John , Stearns Vered , Smith Karen , Armstrong Deborah , Karchin Rachel , Karaindrou Katerina , Zandi Lily , Majcherska Marta , Too Faith , Makell Monique , Lehman Jennifer , Wanchoo Timsy , Wehr Jaime , Conroy Michael , Shiqing Teh. Selina 

TITLE=Druggable genomic landscapes of high-grade gliomas

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1254955

DOI=10.3389/fmed.2023.1254955

ISSN=2296-858X

ABSTRACT=Background: Despite the putatively targetable genomic landscape of high-grade gliomas, the long-term survival benefit of genomically-tailored targeted therapies remains discouraging.Methods: Using glioblastoma (GBM) as a representative example of high-grade gliomas, we evaluated the clonal architecture and distribution of hotspot mutations in 388 GBMs from the Cancer Genome Atlas (TCGA). Mutations were matched with 54 targeted therapies, followed by 14.72 respectively) than patients whose actionable alterations were not targeted (2.83 and 4.2 months respectively). Conclusion: While multiple host, tumor and drug-related features may limit the delivery and efficacy of targeted therapies for patients with high-grade gliomas, genotypematched targeted therapies confer favorable clinical outcomes. Further studies are needed to generate more data on the impact of biochemical features of targeted therapies on their clinical efficacy for high-grade gliomas.