ArticleClinical epigenetics2021
FK228 sensitizes radioresistant small cell lung cancer cells to radiation.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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.
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.
Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Combining [European journal of nuclear medicine and molecular imaging · 2024Article
- Review
- HMGN1 loss sensitizes lung cancer cells to chemotherapy.Scientific reports · 2024Article
- Entinostat Enhances the Efficacy of Chemotherapy in Small Cell Lung Cancer Through S-phase Arrest and Decreased Base Excision Repair.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer.Cell death & disease · 2023Article
- HDAC-an important target for improving tumor radiotherapy resistance.Frontiers in oncology · 2023Review
- PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism: Potential targets to overcome radioresistance in small cell lung cancer.Cancer pathogenesis and therapy · 2023Review
- The Role of MRE11 in the IL-6/STAT3 Pathway of Lung Cancer Cells.Current issues in molecular biology · 2022Article
- The paradigm of drug resistance in cancer: an epigenetic perspective.Bioscience reports · 2022Review
- Promotion of microRNA-146a by histone deacetylase 4 silencing contributes to radiosensitization of esophageal carcinoma.Journal of translational medicine · 2022Article
- Requirements for MRN endonuclease processing of topoisomerase II-mediated DNA damage in mammalian cells.Frontiers in molecular biosciences · 2022Article
- Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [Cancers · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConcurrent thoracic radiation plus chemotherapy is the mainstay of first-line treatment for limited-stage small cell lung cancer (LS-SCLC). Despite initial high responsiveness to combined chemo- and radiotherapy, SCLC almost invariably relapses and develops resistance within one year, leading to poor prognosis in patients with LS-SCLC. Developing new chemical agents that increase ionizing radiation's cytotoxicity against SCLC is urgently needed.
resultsDual histone deacetylase (HDAC) and PI3K inhibitor FK228 not only displayed potent anticancer activity, but also enhanced the therapeutic effects of radiotherapy in SCLC cells. Mechanistically, radioresistant SCLC cells exhibit a lower level of histone H3K9 acetylation and a higher expression level of the MRE11-RAD50-NBS1 (MRN) complex and show more efficient and redundant DNA damage repair capacities than radiosensitive SCLC cells. FK228 pretreatment resulted in marked induction of H3k9 acetylation, attenuated homologous recombination (HR) repair competency and impaired non-homologous end joining (NHEJ) repair efficacy, leading to the accumulation of radiation-induced DNA damage and radiosensitization.
conclusionThe study uncovered that FK228 sensitized human radioresistant SCLC cells to radiation mainly through induction of chromatin decondensation and suppression of DNA damage signaling and repair. Our study provides a rational basis for a further clinical study to test the potential of FK228 as a radiosensitizing agent to increase the radiation-induced tumor cell kill in LS-SCLC patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.