Evidence map›Paper›PMID 34285300›Full record

ArticleScientific reports2021

High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma.

Katja Tuomainen, Aini Hyytiäinen, Ahmed Al-Samadi, Philipp Ianevski, Aleksandr Ianevski, Swapnil Potdar, Laura Turunen, Jani Saarela, Sergey Kuznetsov, Wafa Wahbi and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Prognostic Value of Bcl-xL in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026
    Pooled it
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  8. Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023
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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

14 authors at 4 institutions in 2 countries.

Katja TuomainenDepartment of Oral and Maxillofacial Diseases, University of Helsinki, 00014, Helsinki, Finland. katja.tuomainen@helsinki.fi.
Aini HyytiäinenDepartment of Oral and Maxillofacial Diseases, University of Helsinki, 00014, Helsinki, Finland.
Ahmed Al-SamadiDepartment of Oral and Maxillofacial Diseases, University of Helsinki, 00014, Helsinki, Finland.
Philipp IanevskiInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290, Helsinki, Finland.
Aleksandr IanevskiInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290, Helsinki, Finland.
Swapnil PotdarInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290, Helsinki, Finland.
Laura TurunenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290, Helsinki, Finland.
Jani SaarelaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290, Helsinki, Finland.
Sergey KuznetsovInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290, Helsinki, Finland.
Wafa WahbiDepartment of Oral and Maxillofacial Diseases, University of Helsinki, 00014, Helsinki, Finland.
Maija RisteliCancer and Translational Medicine Research Unit, University of Oulu, 90014, Oulu, Finland.
Antti MäkitieDepartment of Otorhinolaryngology, Head and Neck Surgery, Helsinki University Hospital (HUS), University of Helsinki, 00029, Helsinki, Finland.
Outi MonniApplied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
Tuula SaloDepartment of Oral and Maxillofacial Diseases, University of Helsinki, 00014, Helsinki, Finland.
University of Helsinki · FIHelsinki University Hospital · FIInstitute for Molecular Medicine Finland · FIUniversity of Oulu · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Conventional chemotherapeutic agents are nonselective, often resulting in severe side effects and the development of resistance. Therefore, new molecular-targeted therapies are urgently needed to be integrated into existing treatment regimens. Here, we performed a high-throughput compound screen to identify a synergistic interaction between ionizing radiation and 396 anticancer compounds. The assay was run using five human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) cell lines cultured on the human tumor-derived matrix Myogel. Our screen identified several compounds with strong synergistic and antagonistic effects, which we further investigated using multiple irradiation doses. Navitoclax, which emerged as the most promising radiosensitizer, exhibited synergy with irradiation regardless of the p53 mutation status in all 13 HNSCC cell lines. We performed a live cell apoptosis assay for two representative HNSCC cell lines to examine the effects of navitoclax and irradiation. As a single agent, navitoclax reduced proliferation and induced apoptosis in a dose-dependent manner, whereas the navitoclax-irradiation combination arrested cell cycle progression and resulted in substantially elevated apoptosis. Overall, we demonstrated that combining navitoclax with irradiation resulted in synergistic in vitro antitumor effects in HNSCC cell lines, possibly indicating the therapeutic potential for HNSCC patients.

Indexed as

Radiation, IonizingAniline CompoundsAntineoplastic AgentsApoptosisCell Line, TumorHead and Neck NeoplasmsHigh-Throughput Screening AssaysHuman papillomavirus 16HumansMutationSquamous Cell Carcinoma of Head and NeckSulfonamidesTumor Suppressor Protein p53Aniline CompoundsAntineoplastic AgentsnavitoclaxSulfonamidesTumor Suppressor Protein p53

Identifiers

PMID34285300
PMCPMC8292418
OpenAlexW3183825217

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.