Evidence map›Paper›PMID 35260696›Full record

ArticleScientific reports2022

CX-5461 induces radiosensitization through modification of the DNA damage response and not inhibition of RNA polymerase I.

Stacey L Lehman, Kayla R Schwartz, Shrankhla Maheshwari, Kevin Camphausen, Philip J Tofilon

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Radiosensitization of Glioblastoma by the K-ras Inhibitor RMC-6236.bioRxiv : the preprint server for biology · 2026
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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

5 authors at 1 institution in 1 country.

Stacey L LehmanRadiation Oncology Branch, National Cancer Institute, 10 Center Drive-MSC 1002, Building 10, B3B69B, Bethesda, MD, 20892, USA.
Kayla R SchwartzRadiation Oncology Branch, National Cancer Institute, 10 Center Drive-MSC 1002, Building 10, B3B69B, Bethesda, MD, 20892, USA.
Shrankhla MaheshwariRadiation Oncology Branch, National Cancer Institute, 10 Center Drive-MSC 1002, Building 10, B3B69B, Bethesda, MD, 20892, USA.
Kevin CamphausenRadiation Oncology Branch, National Cancer Institute, 10 Center Drive-MSC 1002, Building 10, B3B69B, Bethesda, MD, 20892, USA.
Philip J TofilonRadiation Oncology Branch, National Cancer Institute, 10 Center Drive-MSC 1002, Building 10, B3B69B, Bethesda, MD, 20892, USA. philip.tofilon@nih.gov.
National Cancer Institute · US

Funding

Pre-clinical Development of Radiation Sensitizers for Patients with GlioblastomaZIASC010372 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI CAMPHAUSEN, KEVIN · 2009 to 2025
$12.0M
Radiation-induced translational control of gene expressionZIABC011373 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TOFILON, PHILIP · 2011 to 2025
$11.7M
Intramural NIH HHS ZIA BC011373
6 · The paper itself

Abstract

Increased ribosome biogenesis is a distinguishing feature of cancer cells, and small molecule inhibitors of ribosome biogenesis are currently in clinical trials as single agent therapy. It has been previously shown that inhibiting ribosome biogenesis through the inhibition of nuclear export of ribosomal subunits sensitizes tumor cells to radiotherapy. In this study, the radiosensitizing potential of CX-5461, a small molecule inhibitor of RNA polymerase I, was tested. Radiosensitization was measured by clonogenic survival assay in a panel of four tumor cell lines derived from three different tumor types commonly treated with radiation. 50 nM CX-5461 radiosensitized PANC-1, U251, HeLa, and PSN1 cells with dose enhancement factors in the range of 1.2-1.3. However, 50 nM CX-5461 was not sufficient to inhibit 45S transcription alone or in combination with radiation. The mechanism of cell death with the combination of CX-5461 and radiation occurred through mitotic catastrophe and not apoptosis. CX-5461 inhibited the repair and/or enhanced the initial levels of radiation-induced DNA double strand breaks. Understanding the mechanism of CX-5461-induced radiosensitization should be of value in the potential application of the CX-5461/radiotherapy combination in cancer treatment.

Indexed as

BenzothiazolesNaphthyridinesRadiation-Sensitizing AgentsRNA Polymerase IApoptosisCell Line, TumorDNA Breaks, Double-StrandedDNA DamageHumansBenzothiazolesCX 5461NaphthyridinesRadiation-Sensitizing AgentsRNA Polymerase I

Identifiers

PMID35260696
PMCPMC8904802
OpenAlexW4220744042

What Socratic holds

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LicenceCC BY
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 Socratic graph.