Response to Letter to the Editor by Yang et al

Our plain-English summary of Response to Letter to the Editor by Yang et al, by R. Hassan, M. Sengupta, J. Murai, et al (Journal of Thoracic Oncology, 2020).

The study

• Authors: R. Hassan, M. Sengupta, J. Murai, Y. Pommier
• Journal: Journal of Thoracic Oncology
• Published: 2020;15(6):e91
• Type of article: Letter, Comment
• Read it: PubMed · Publisher

In plain English

This is a short reply letter by the authors to a letter from Yang et al. It reports no new experiments. In earlier published work, the authors had reported that BAP1 expression did not determine how sensitive mesothelioma cell lines (cancer cells grown in the laboratory) were to PARP inhibitors, a class of cancer drugs. The letter describes Yang et al.'s analysis of a public database covering 20 malignant pleural mesothelioma cell lines, eight with BAP1 mutations and 12 without, tested against olaparib, talazoparib, rucaparib and veliparib. According to the letter, Yang et al. found that drug-sensitive cell lines included both types, some BAP1-mutant cells were highly resistant to several of these drugs, and response was not correlated with BAP1 status. The authors concluded that both their work and Yang et al.'s show sensitivity of mesothelioma cells to these drugs is independent of BAP1 status. They noted two open questions: whether this holds in other cancers such as bladder and renal cancers, and whether SLFN11 expression predicts response in patients. They said an ongoing olaparib trial will help define the drugs' role, if any, in treating mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Letter to the editor (the authors' reply to another letter); no new study data
• Who was studied: No new study population. The letter discusses mesothelioma cell lines from the authors' earlier paper. It also discusses Yang et al.'s analysis of 20 malignant pleural mesothelioma cell lines from the Genomics of Drug Sensitivity in Cancer database: 8 BAP1-mutant and 12 BAP1-wild type.
• Exposure: Not asbestos. The letter concerns laboratory sensitivity of mesothelioma cell lines to the PARP inhibitor drugs olaparib, talazoparib, rucaparib and veliparib, in relation to BAP1 mutation status.
• Main results:
  • In their earlier published work (not this letter), the authors reported that BAP1 expression did not determine the sensitivity of mesothelioma cell lines to PARP inhibitors.
  • As described in this letter, Yang et al. found that PARP inhibitor-sensitive malignant pleural mesothelioma cell lines included both BAP1-mutant and BAP1-wild type cells.
  • As described in this letter, Yang et al. found that some BAP1-mutant malignant pleural mesothelioma cells were highly resistant to multiple PARP inhibitors.
  • Yang et al. concluded that the response of malignant pleural mesothelioma cell lines to PARP inhibitors is highly heterogeneous and not correlated with BAP1 mutation status.
  • The authors noted an ongoing clinical trial of olaparib (NCT03531840) that they said will help define the role of PARP inhibitors, if any, in treating mesothelioma.
• The authors' conclusion: The authors concluded that their work and Yang et al.'s show that the sensitivity of mesothelioma cells to PARP inhibitors is independent of the cells' BAP1 mutation status.
• Limitations the authors state:
  • The authors said it is unanswered whether the lack of correlation is specific to mesothelioma or also true in other cancers with frequent BAP1 mutations, such as bladder and renal cancers.
  • The authors said it remains to be tested whether SLFN11 expression predicts response to PARP inhibitors in patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

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