Evidence map›Paper›PMID 34063457›Full record

ArticleCancers2021

The Individual Effects of Cyclin-Dependent Kinase Inhibitors on Head and Neck Cancer Cells-A Systematic Analysis.

Nina Schoenwaelder, Inken Salewski, Nadja Engel, Mareike Krause, Björn Schneider, Michael Müller, Christin Riess, Heiko Lemcke, Anna Skorska, Christina Grosse-Thie and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

12 authors at 1 institution in 1 country.

Nina SchoenwaelderDepartment of Internal Medicine, Medical Clinic III-Hematology, Oncology, Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany.
Inken SalewskiDepartment of Internal Medicine, Medical Clinic III-Hematology, Oncology, Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany.
Nadja EngelDepartment of Oral and Maxillofacial Surgery, Facial Plastic Surgery, University Medical Center Rostock, 18057 Rostock, Germany.ORCID 0000-0002-6362-9282
Mareike KrauseDepartment of Internal Medicine, Medical Clinic III-Hematology, Oncology, Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany.ORCID 0000-0002-5553-6828
Björn SchneiderInstitute of Pathology, University Medical Center Rostock, Strempelstr.14, 18057 Rostock, Germany.ORCID 0000-0002-0282-7330
Michael MüllerCore Facility for Cell Sorting & Cell Analysis, Laboratory for Clinical Immunology, University Medical Center Rostock, 18057 Rostock, Germany.
Christin RiessDepartment of Internal Medicine, Medical Clinic III-Hematology, Oncology, Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany.ORCID 0000-0002-1994-4779
Heiko LemckeDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University Medical Center Rostock, 18057 Rostock, Germany.ORCID 0000-0003-2821-2323
Anna SkorskaDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University Medical Center Rostock, 18057 Rostock, Germany.ORCID 0000-0001-6287-4916
Christina Grosse-ThieDepartment of Internal Medicine, Medical Clinic III-Hematology, Oncology, Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany.ORCID 0000-0002-8128-0125
Christian JunghanssDepartment of Internal Medicine, Medical Clinic III-Hematology, Oncology, Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany.
Claudia MaletzkiDepartment of Internal Medicine, Medical Clinic III-Hematology, Oncology, Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany.ORCID 0000-0002-8389-8439
University of Rostock · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclin-dependent kinase inhibitors (CDKi´s) display cytotoxic activity against different malignancies, including head and neck squamous cell carcinomas (HNSCC). By coordinating the DNA damage response, these substances may be combined with cytostatics to enhance cytotoxicity. Here, we investigated the influence of different CDKi´s (palbociclib, dinaciclib, THZ1) on two HNSCC cell lines in monotherapy and combination therapy with clinically-approved drugs (5-FU, Cisplatin, cetuximab). Apoptosis/necrosis, cell cycle, invasiveness, senescence, radiation-induced γ-H2AX DNA double-strand breaks, and effects on the actin filament were studied. Furthermore, the potential to increase tumor immunogenicity was assessed by analyzing Calreticulin translocation and immune relevant surface markers. Finally, an in vivo mouse model was used to analyze the effect of dinaciclib and Cisplatin combination therapy. Dinaciclib, palbociclib, and THZ1 displayed anti-neoplastic activity after low-dose treatment, while the two latter substances slightly enhanced radiosensitivity. Dinaciclib decelerated wound healing, decreased invasiveness, and induced MHC-I, accompanied by high amounts of surface-bound Calreticulin. Numbers of early and late apoptotic cells increased initially (24 h), while necrosis dominated afterward. Antitumoral effects of the selective CDKi palbociclib were weaker, but combinations with 5-FU potentiated effects of the monotherapy. Additionally, CDKi and CDKi/chemotherapy combinations induced MHC I, indicative of enhanced immunogenicity. The in vivo studies revealed a cell line-specific response with best tumor growth control in the combination approach. Global acting CDKi's should be further investigated as targeting agents for HNSCC, either individually or in combination with selected drugs. The ability of dinaciclib to increase the immunogenicity of tumor cells renders this substance a particularly interesting candidate for immune-based oncological treatment regimens.

Indexed as

combination strategiesimmunogenic cell deathtargeted therapyxenograft model

Identifiers

PMID34063457
PMCPMC8157193
OpenAlexW3161558405

What Socratic 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 Socratic graph.