Evidence map›Paper›PMID 26086472›Full record

ArticlePloS one2015

Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells.

Markus Hecht, Sonja Erber, Thomas Harrer, Hartwig Klinker, Thomas Roth, Hans Parsch, Nora Fiebig, Rainer Fietkau, Luitpold V Distel

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Approaches to repurposing reverse transcriptase antivirals in cancer.British journal of clinical pharmacology · 2025
    Review
  6. Article
  7. Article
  8. Antiretroviral Drugs Impact Autophagy: Opportunities for Drug Repurposing.Frontiers in bioscience (Landmark edition) · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Evolution of Antiretroviral Drug Rilpivirine and Approach to Oncology.International journal of molecular sciences · 2023
    Review
  14. Review
  15. Review
  16. An EpigeneticInternational journal of molecular sciences · 2022
    Review
  17. CombinedPharmaceuticals (Basel, Switzerland) · 2022
    Article
  18. Article
  19. Paclitaxel-induced stress granules increaseJournal of biomedical research · 2021
    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 2 institutions in 1 country.

Markus HechtDepartment of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
Sonja ErberDepartment of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
Thomas HarrerDepartment of Internal Medicine 3, University Hospital Erlangen, Erlangen, Germany.
Hartwig KlinkerDepartment of Internal Medicine 2, University Hospital Würzburg, Würzburg, Germany.
Thomas RothCentral Laboratory, University Hospital Erlangen, Erlangen, Germany.
Hans ParschCentral Laboratory, University Hospital Erlangen, Erlangen, Germany.
Nora FiebigDepartment of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
Rainer FietkauDepartment of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
Luitpold V DistelDepartment of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
Universitätsklinikum Erlangen · DEUniversitätsklinikum Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI) Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo.

methodsCytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50) were calculated and compared to the blood levels in our patients and published data.

resultsThe in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 μmol/l (= 9944 ng/ml), Nevirapine 239 μmol/l (= 63,786 ng/ml), Etravirine 89.0 μmol/l (= 38,740 ng/ml), Lersivirine 543 μmol/l (= 168,523 ng/ml), Delavirdine 171 μmol/l (= 78,072 ng/ml), Rilpivirine 24.4 μmol/l (= 8941 ng/ml). As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml), of Rilpivirine 144 ng/ml (range 0-572 ng/ml) and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml). Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients.

conclusionAll studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic cancer incidence might be reduced. Efavirenz might be a new option in the treatment of cancer.

Indexed as

AlkynesAntineoplastic AgentsBenzoxazinesCell Line, TumorCell ProliferationCell SurvivalCyclopropanesDrug Screening Assays, AntitumorHIV-1HIV InfectionsHumansInhibitory Concentration 50Pancreatic NeoplasmsReverse Transcriptase InhibitorsAlkynesAntineoplastic AgentsBenzoxazinesCyclopropanesefavirenzReverse Transcriptase Inhibitors

Identifiers

PMID26086472
PMCPMC4473268
OpenAlexW2308583034

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.