Molecular targets in malignant pleural mesothelioma treatment

Our plain-English summary of Molecular targets in malignant pleural mesothelioma treatment, by G. Pasello, A. Favaretto (Current Drug Targets, 2009).

The study

• Authors: G. Pasello, A. Favaretto
• Journal: Current Drug Targets
• Published: 2009;10(12):1235-44
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is an aggressive tumour of the serosal surfaces with poor prognosis and increasing incidence due to widespread previous asbestos exposure. Relative chemotherapeutic and radiotherapeutic resistance makes malignant pleural mesothelioma (MPM) difficult to manage, even though encouraging results were achieved with multimodality treatment. Better knowledge of angiogenesis and molecular pathways involved in MPM seems to be the right way to define new targets for systemic treatment. Neoangiogenesis may be considered as a critical step in the development of mesothelioma. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are autocrine growth factors in MPM and epidermal growth factor receptor (EGFR) appears highly expressed in this tumour. Tyrosine kinase inhibitors (TKIs) targeting growth factors like vandetanib, dasatinib, and angiogenesis inhibitors like bevacizumab, are among the most promising agents under evaluation in clinical trials. Mesothelioma is a malignancy which owes its chemoresistance to an apoptotic defect. Thus the introduction of new biologic drugs like vorinostat, bortezomib, everolimus and temsirolimus, in the treatment of MPM finds a strong rationale. This review focuses on the current target therapies and evaluates future biologic approaches for the systemic management of MPM.

In plain English

This 2009 article was a narrative review of targeted drug treatments for malignant pleural mesothelioma, not an original study. It described the tumour's biology and summarised published and ongoing trials of drugs aimed at blood-vessel growth, growth-factor receptors and cell-death pathways. The article does not describe how studies were chosen. Among the results it reported from other researchers: a randomized phase II trial found no statistically significant difference in progression-free or overall survival when bevacizumab was added to cisplatin and gemcitabine; three phase II trials of imatinib given alone showed no objective response; and a phase III trial of doxorubicin with or without ranpirnase in 428 patients found no statistically significant difference between the two arms. In that trial a survival difference was seen only in a subgroup of 130 previously treated patients (median 10.5 vs. 9 months, p= 0.033). The authors concluded that, because mesothelioma's resistance to chemotherapy comes from a defect in programmed cell death (apoptosis), newer biologic drugs have a strong rationale.

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 current and future targeted therapies for malignant pleural mesothelioma (no original data; no search method described)
• Who was studied: Published first- and second-line clinical trials (summarised in Table 1), ongoing phase II and III trials (Table 2), and laboratory studies of targeted drugs in malignant pleural mesothelioma
• Exposure: Not an exposure study; the subject is drug treatment. The introduction mentions asbestos as background, as the cause of most cases of malignant pleural mesothelioma, citing other work
• Main results:
  • The review reported that a double-blind, placebo-controlled randomized phase II trial of cisplatin plus gemcitabine with or without bevacizumab found no statistically significant difference in progression-free survival or overall survival between the two arms
  • The review reported that three phase II trials of imatinib mesylate given as a single agent showed no objective response in patients with malignant pleural mesothelioma
  • The review reported that a Cancer and Leukemia Group B phase II trial of gefitinib showed no activity in patients with malignant pleural mesothelioma, even though 97% of cases overexpressed EGFR
  • The review reported that a phase III trial of doxorubicin with or without ranpirnase in 428 patients found no statistically significant difference between the arms. A survival effect was seen only in a subgroup of 130 previously treated patients: median survival 10.5 months with ranpirnase vs. 9 months without (p= 0.033)
  • The review reported that cediranib, tested in a Southwest Oncology Group phase II trial, showed a disease control rate of 42%, a median progression-free survival of 3 months and a median survival of 10 months
• The authors' conclusion: The authors concluded that mesothelioma owes its resistance to chemotherapy to an apoptotic defect, so biologic drugs such as vorinostat, bortezomib, everolimus and temsirolimus have a strong rationale. They also concluded that targeting multiple molecular pathways, or combining targeted and cytotoxic drugs, seems a valid approach.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Malignant Mesothelioma, Serosal Surface, Prognosis, Asbestos Exposure, Angiogenesis, Mesothelioma, Platelet-Derived Growth Factor (PDGF).

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