Combining Chemotherapeutic Agents, Targeted Therapies, Vaccines and Natural Bioactive Compounds for Mesothelioma: Advances and Perspectives

Our plain-English summary of Combining Chemotherapeutic Agents, Targeted Therapies, Vaccines and Natural Bioactive Compounds for Mesothelioma: Advances and Perspectives, by R. Carrano, C. Zucca, N. Cristina, et al (Oncology Research, 2025).

The study

• Authors: R. Carrano, C. Zucca, N. Cristina, M. Grande, E.L. Maggio, R. Bei, A. Infante, C. Focaccetti, V. Lucarini, L. Cifaldi, L. Masuelli, L. Mutti, C. Palumbo, M. Benvenuto, R. Bei
• Journal: Oncology Research
• Published: 2025;33(9):2181-2204
• Type of article: Review
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options. Despite recent advances, conventional treatment approaches remain largely ineffective due to late diagnosis, chemoresistance and immunosuppressive tumor microenvironment. This review reports the latest studies on combination therapies for mesothelioma, focusing on the potential of integrating chemotherapeutic agents, molecularly targeted agents, vaccines and natural bioactive compounds such as polyphenols. Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients. Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments. Moreover, natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance. While several combination strategies are under clinical investigation, further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.

© 2025 The Authors.

In plain English

This review covered laboratory, animal and clinical studies combining chemotherapy, targeted drugs, vaccines and plant compounds called polyphenols against mesothelioma. Unless stated otherwise, mesothelioma meant pleural mesothelioma. In a phase III trial of 440 patients, overall survival was 17.3 months with pembrolizumab plus chemotherapy versus 16.1 months with chemotherapy alone. In the MAPS trial of 448 patients, median overall survival was 18.8 months with bevacizumab plus chemotherapy versus 16.1 months with chemotherapy alone. That regimen has been recommended in Europe as a first-line option for unresectable mesothelioma. Adding nintedanib to chemotherapy did not improve progression-free survival. In the DENIM trial, a dendritic-cell treatment did not improve overall survival over best supportive care. Polyphenols such as curcumin had been combined with cancer drugs only in cell lines and animals, not in mesothelioma patients. The authors noted that many trials were early-phase or small. They also noted that little of an oral polyphenol reaches the bloodstream, partly because the liver and gut break it down quickly. The authors concluded that further studies are needed to validate these findings and translate them into standardized treatment protocols.

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: Review of published preclinical (cell line and animal) studies and clinical trials on combination therapies for mesothelioma
• Who was studied: No population of its own. The review covered mesothelioma cell lines, mouse models and clinical trials in mesothelioma patients. The term mesothelioma refers to pleural mesothelioma unless another origin (e.g., peritoneal) is specified.
• Exposure: Not an asbestos exposure study. Asbestos is mentioned only as background, as the leading risk factor. The interventions reviewed were combinations of chemotherapy (e.g., cisplatin/pemetrexed), targeted drugs (immune checkpoint antibodies, angiogenesis inhibitors, others), vaccines and polyphenols.
• Main results:
  • In a reviewed phase III randomized trial of 440 mesothelioma patients, overall survival was 17.3 months with pembrolizumab plus chemotherapy vs. 16.1 months with chemotherapy alone. The 3-year overall survival rate was 25% vs. 17%.
  • In the reviewed MAPS phase III trial (448 patients), median overall survival was 18.8 months with chemotherapy plus bevacizumab vs. 16.1 months with chemotherapy alone.
  • Based on the MAPS results, the cisplatin/pemetrexed/bevacizumab regimen has been recommended in Europe as a first-line option for patients with unresectable mesothelioma.
  • In the reviewed LUME-Meso phase III trial, adding nintedanib to standard chemotherapy did not improve progression-free survival.
  • In the reviewed ATOMIC-Meso trial (249 participants, chemotherapy-naive patients with unresectable non-epithelioid mesothelioma), overall survival was 9.3 months with ADI-PEG20 plus chemotherapy vs. 7.7 months with placebo plus chemotherapy.
  • In the reviewed single-arm DREAM phase II trial of cisplatin/pemetrexed plus durvalumab, the primary endpoint (progression-free survival at 6 months) was met by 31 of 54 patients.
  • In the reviewed DENIM trial in pleural mesothelioma, MesoPher dendritic cells given as maintenance therapy after chemotherapy did not improve overall survival compared with best supportive care alone.
  • Combinations of polyphenols with chemotherapy had not yet been tested clinically in mesothelioma patients. The reviewed polyphenol evidence came from cell lines and animal models.
• The authors' conclusion: The authors concluded that some trials of combination approaches showed encouraging results, but further studies are needed to validate the findings and translate them into standardized treatment protocols.
• Limitations the authors state:
  • Many of the clinical trials reviewed were early-phase or had small sample sizes.
  • Most polyphenol studies were done in cell lines or animal models that do not fully reflect human disease.
  • Polyphenols have low oral bioavailability, which limits their potential use as treatments. The authors attribute this partly to rapid metabolism in the liver and gastrointestinal tract, poor solubility in water, and interactions with food.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Prognosis, Tumor Microenvironment, Chemotherapy, Synergistic Effect.

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• Targeted therapies in malignant pleural mesothelioma: a review of clinical studies — L. Greillier, S. Marco, et al. (2011)
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