RT Journal Article
T1 Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma.
A1 Aguilar-Morante, Diana
A1 Gómez-Cabello, Daniel
A1 Quek, Hazel
A1 Liu, Tianqing
A1 Hamerlik, Petra
A1 Lim, Yi Chieh
K1 CNS tumors
K1 DNA damage response
K1 DNA repair
K1 glioma
K1 molecular markers
K1 pharmacotherapeutics
K1 precision medicine
K1 synthetic lethality
K1 targeted therapy
AB 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.
SN 2227-9059
YR 2022
FD 2022-01-31
LK http://hdl.handle.net/10668/20816
UL http://hdl.handle.net/10668/20816
LA en
DS RISalud
RD Apr 18, 2025