Evidence map›Paper›PMID 33738447›Full record

ReviewNeuro-oncology advances

The promise of DNA damage response inhibitors for the treatment of glioblastoma.

Nazanin K Majd, Timothy A Yap, Dimpy Koul, Veerakumar Balasubramaniyan, Xiaolong Li, Sabbir Khan, Katilin S Gandy, W K Alfred Yung, John F de Groot

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Nazanin K MajdDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Timothy A YapDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Dimpy KoulDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Veerakumar BalasubramaniyanDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Xiaolong LiDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sabbir KhanDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Katilin S GandyDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
W K Alfred YungDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
John F de GrootDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas MD Anderson Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM), the most aggressive primary brain tumor, has a dismal prognosis. Despite our growing knowledge of genomic and epigenomic alterations in GBM, standard therapies and outcomes have not changed significantly in the past two decades. There is therefore an urgent unmet need to develop novel therapies for GBM. The inter- and intratumoral heterogeneity of GBM, inadequate drug concentrations in the tumor owing to the blood-brain barrier, redundant signaling pathways contributing to resistance to conventional therapies, and an immunosuppressive tumor microenvironment, have all hindered the development of novel therapies for GBM. Given the high frequency of DNA damage pathway alterations in GBM, researchers have focused their efforts on pharmacologically targeting key enzymes, including poly(ADP-ribose) polymerase (PARP), DNA-dependent protein kinase, ataxia telangiectasia-mutated, and ataxia telangiectasia and Rad3-related. The mainstays of GBM treatment, ionizing radiation and alkylating chemotherapy, generate DNA damage that is repaired through the upregulation and activation of DNA damage response (DDR) enzymes. Therefore, the use of PARP and other DDR inhibitors to render GBM cells more vulnerable to conventional treatments is an area of intense investigation. In this review, we highlight the growing body of data behind DDR inhibitors in GBM, with a focus on putative predictive biomarkers of response. We also discuss the challenges involved in the successful development of DDR inhibitors for GBM, including the intracranial location and predicted overlapping toxicities of DDR agents with current standards of care, and propose promising strategies to overcome these hurdles.

Indexed as

DDR inhibitorsglioblastomaMGMT methylationradiationtemozolomide

Identifiers

PMID33738447
PMCPMC7954093
OpenAlexW3129021569

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.