TY - JOUR
T1 - Targeting the DNA damage response to overcome cancer drug resistance in glioblastoma
AU - Ferri, Alessandra
AU - Stagni, Venturina
AU - Barilà, Daniela
N1 - Funding Information:
This research was funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC)-IG2016-n.19069, MIUR-JPI-HDHL-NUTRICOG-MiTyrAge, PRIN_2015LZE994_005, and the Italian Ministry of Health, RF-2016-02362022 to D.B. A.F. is funded by the PhD programme in Molecular and Cellular Biology, University of Rome Tor Vergata. The study was supported for V.S. by a research grant from Italian Ministry of Health RF-2016-02363460. We acknowledge all our laboratory members for critical reading of the manuscript.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/2
Y1 - 2020/7/2
N2 - Glioblastoma multiforme (GBM) is a severe brain tumor whose ability to mutate and adapt to therapies is at the base for the extremely poor survival rate of patients. Despite multiple efforts to develop alternative forms of treatment, advances have been disappointing and GBM remains an arduous tumor to treat. One of the leading causes for its strong resistance is the innate upregulation of DNA repair mechanisms. Since standard therapy consists of a combinatory use of ionizing radiation and alkylating drugs, which both damage DNA, targeting the DNA damage response (DDR) is proving to be a beneficial strategy to sensitize tumor cells to treatment. In this review, we will discuss how recent progress in the availability of the DDR kinase inhibitors will be key for future therapy development. Further, we will examine the principal existing DDR inhibitors, with special focus on those currently in use for GBM clinical trials.
AB - Glioblastoma multiforme (GBM) is a severe brain tumor whose ability to mutate and adapt to therapies is at the base for the extremely poor survival rate of patients. Despite multiple efforts to develop alternative forms of treatment, advances have been disappointing and GBM remains an arduous tumor to treat. One of the leading causes for its strong resistance is the innate upregulation of DNA repair mechanisms. Since standard therapy consists of a combinatory use of ionizing radiation and alkylating drugs, which both damage DNA, targeting the DNA damage response (DDR) is proving to be a beneficial strategy to sensitize tumor cells to treatment. In this review, we will discuss how recent progress in the availability of the DDR kinase inhibitors will be key for future therapy development. Further, we will examine the principal existing DDR inhibitors, with special focus on those currently in use for GBM clinical trials.
KW - DDR inhibitors
KW - DNA damage response
KW - Glioblastoma
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U2 - 10.3390/ijms21144910
DO - 10.3390/ijms21144910
M3 - Review article
C2 - 32664581
AN - SCOPUS:85087795139
VL - 21
SP - 1
EP - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 14
M1 - 4910
ER -