"One marker does not fit all": additional translational and validation studies are needed to identify faithful predictors of pemetrexed activity in mesothelioma

Our plain-English summary of "One marker does not fit all": additional translational and validation studies are needed to identify faithful predictors of pemetrexed activity in mesothelioma, by E. Giovannetti, G.J. Peters, P.A. Zucali (Journal of Thoracic Oncology, 2013).

The study

• Authors: E. Giovannetti, G.J. Peters, P.A. Zucali
• Journal: Journal of Thoracic Oncology
• Published: 2013;8(8):e79-80
• Type of article: Letter, Comment
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This article is a letter to the editor, not a new study, and it reports no new patient data. It commented on a study by Mairinger and colleagues that used immunohistochemistry and quantitative PCR to measure the expression of five folate pathway genes in 63 malignant pleural mesotheliomas treated with pemetrexed, a chemotherapy drug. As the letter described it, that study suggested overall survival was associated with high reduced folate carrier and low FPGS mRNA levels but not with thymidylate synthase (TS), and found no significant association with tumor response. The letter's authors contrasted this with their own earlier study of 99 patients given carboplatin and pemetrexed, which linked TS mRNA and protein levels to overall survival. They also cited another study of 85 patients that found no correlation for TS or FPGS protein. They suggested reasons for the differences, noting that the Mairinger study's FPGS antibody had not been tested in cells that overproduce or lack FPGS, and that FPGS mRNA undergoes extensive splicing. The authors concluded that cross-laboratory validation of techniques, and larger, uniformly treated patient groups, are needed to identify reliable markers.

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 commenting on a published study (no new data)
• Who was studied: No population studied by the authors. The letter discusses a published study of 63 malignant pleural mesothelioma tumors from pemetrexed-treated patients, and other published patient studies.
• Exposure: Pemetrexed-based chemotherapy for malignant pleural mesothelioma; asbestos exposure is not discussed
• Main results:
  • As described by the letter, the Mairinger et al. study found an association with overall survival for folate pathway markers but not for thymidylate synthase (TS), and no significant association with objective response
  • The letter's authors cited their own earlier published study, which reported a correlation of TS mRNA and protein expression with overall survival in 99 malignant pleural mesothelioma patients given carboplatin plus pemetrexed
  • The letter cited another recent study reporting no correlation of TS or FPGS protein expression in 85 patients receiving pemetrexed
  • The authors noted that the FPGS antibody used in the Mairinger et al. study had not been tested in FPGS-overexpressing or FPGS-deficient cells
  • The authors suggested FPGS mRNA splicing might explain the unexpected link between low FPGS and longer survival
• The authors' conclusion: The authors concluded that interlaboratory validation of sample collection and analysis techniques, together with larger, uniformly treated patient populations, is needed to validate the best markers for personalized treatment of malignant pleural mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Mesothelioma.

Related studies

• New tricks for old biomarkers: thymidylate synthase expression as a predictor of pemetrexed activity in malignant mesothelioma — P.A. Zucali, E. Giovannetti, et al. (2010)
• Reduced folate carrier and folylpolyglutamate synthetase, but not thymidylate synthase predict survival in pemetrexed-treated patients suffering from malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• The issue of studies evaluating biomarkers which predict outcome after pemetrexed-based chemotherapy in malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma: The Nancy Centre of Biological Resources' Mesothelioma Cohort — F. Vlastos, G. Hillas, et al. (2009)
• Adaptation of a chemosensitivity assay to accurately assess pemetrexed in ex vivo cultures of lung cancer — S.L. Suchy, R.J. Landreneau, et al. (2013)
• Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma — D.E. Lustgarten, C. Deshpande, et al. (2013)

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