Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma

Our plain-English summary of Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma, by B. Biersack (Non-coding RNA Research, 2018).

The study

• Author: B. Biersack
• Journal: Non-coding RNA Research
• Published: 2018;3(4):213-225
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Gemcitabine and pemetrexed are clinically approved antimetabolites for the therapy of mesothelioma diseases. These drugs are often applied in combination with platinum complexes and other drugs. The activity of antimetabolites depended on the expression levels of certain non-coding RNAs, in particular, of small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The development of tumor resistance towards antimetabolites was regulated by non-coding RNAs. An overview of the interplay between gemcitabine/pemetrexed antimetabolites and non-coding RNAs in mesothelioma is provided. Further to this, various non-coding RNA-modulating agents are discussed which displayed positive effects on gemcitabine or pemetrexed treatment of mesothelioma diseases. A detailed knowledge of the connections of non-coding RNAs with antimetabolites will be constructive for the design of improved therapies in future.

In plain English

This article was a narrative review by a single author, not a new study of patients or workers. It gathered published research on how RNA molecules that do not make proteins, both small microRNAs and long non-coding RNAs, relate to two approved mesothelioma chemotherapy drugs, gemcitabine and pemetrexed. The article did not study asbestos exposure; asbestos came up only as background and in brief mentions of asbestos-related lung cancer and asbestos-exposed people. Among findings reported by other researchers, restoring miR-16 made malignant pleural mesothelioma cells more sensitive to gemcitabine. Raising miR-145 increased the activity of pemetrexed against such cells. Tumor samples taken after pemetrexed plus cisplatin therapy showed lower miR-210 than untreated samples. The author noted that most gemcitabine-related findings came from pancreas and lung cancer samples. The review also listed plant compounds, vitamins and drugs reported to change these RNAs. It urged caution about one drug group, HDAC inhibitors, which sometimes had unwanted effects. The author concluded that these RNAs can either sensitize or harden cancer cells to the two drugs, and called for more research.

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: Narrative review of published studies (no new data collected)
• Who was studied: No study population of its own. It drew on published studies of mesothelioma tissue, blood and cell lines, and on studies of other cancers such as pancreatic, lung and breast cancer.
• Exposure: The chemotherapy drugs gemcitabine and pemetrexed, plus agents reported to modify non-coding RNAs. Asbestos exposure was not studied.
• Main results:
  • Reviewed finding from a cited study: restoring miR-16 sensitized malignant pleural mesothelioma (MPM) cells to gemcitabine.
  • Reviewed finding from a cited study: upregulating miR-145 enhanced the activity of pemetrexed against MPM cells.
  • Reviewed finding from a cited study: miR-210 was downregulated in samples after pemetrexed plus cisplatin therapy, compared with therapy-naive samples.
  • Reviewed finding from a cited study: patients with high NEAT1 expression had longer overall survival if they had not received induction chemotherapy.
  • Reviewed finding from a cited study: miR-202 was suppressed in asbestos-related lung cancer.
  • Reviewed finding from a cited study: miR-1281 is upregulated in MPM patients and asbestos-exposed people.
• The authors' conclusion: The author concluded that non-coding RNAs can modulate gemcitabine and pemetrexed activity in mesothelioma, either sensitizing or hardening cancer cells to these drugs, and that more research is needed.
• Limitations the authors state:
  • Most of the gemcitabine-related findings reviewed came from pancreas and lung cancer samples rather than mesothelioma.
  • HDAC inhibitors can sometimes suppress tumor-suppressor microRNAs or induce oncogenic ones, so caution and more research are needed before combining them with these drugs.

Topics

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

Related studies

• Relations between approved platinum drugs and non-coding RNAs in mesothelioma — B. Biersack (2018)
• Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM) — C.M. Wright, M.B. Kirschner, et al. (2013)
• The role of non-coding RNAs in pleural mesothelioma — G. Tonnini, G. Di Mauro, et al. (2025)
• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma — G. Ak, S. Metintas, et al. (2015)
• A phase II study of the combination of gemcitabine and imatinib mesylate in pemetrexed-pretreated patients with malignant pleural mesothelioma — P.A. Zucali, M. Perrino, et al. (2020)

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