NDLI: Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma

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Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma

Content Provider	MDPI
Author	Daniel, Gómez-Cabello Aguilar-Morante, Diana Quek, Hazel Liu, Tianqing Hamerlik, Petra Lim, Yi Chieh
Copyright Year	2022
Description	Adult diffuse glioma, particularly glioblastoma (GBM), is a devastating tumor of the central nervous system. The existential threat of this disease requires on-going treatment to counteract tumor progression. The present outcome is discouraging as most patients will succumb to this disease. The low cure rate is consistent with the failure of first-line therapy, radiation and temozolomide (TMZ). Even with their therapeutic mechanism of action to incur lethal DNA lesions, tumor growth remains undeterred. Delivering additional treatments only delays the inescapable development of therapeutic tolerance and disease recurrence. The urgency of establishing lifelong tumor control needs to be re-examined with a greater focus on eliminating resistance. Early genomic and transcriptome studies suggest each tumor subtype possesses a unique molecular network to safeguard genome integrity. Subsequent seminal work on post-therapy tumor progression sheds light on the involvement of DNA repair as the causative contributor for hypermutation and therapeutic failure. In this review, we will provide an overview of known molecular factors that influence the engagement of different DNA repair pathways, including targetable vulnerabilities, which can be exploited for clinical benefit with the use of specific inhibitors.
Starting Page	332
e-ISSN	22279059
DOI	10.3390/biomedicines10020332
Journal	Biomedicines
Issue Number	2
Volume Number	10
Language	English
Publisher	MDPI
Publisher Date	2022-01-31
Access Restriction	Open
Subject Keyword	Biomedicines Glioma Dna Damage Response Dna Repair Synthetic Lethality Precision Medicine Targeted Therapy Cns Tumors Molecular Markers Pharmacotherapeutics
Content Type	Text
Resource Type	Article

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