Current and prospective pharmacotherapies for the treatment of pleural mesothelioma

ABSTRACT

Introduction: Mesothelioma is a rare asbestos-linked cancer with an expected incidence peak between 2015–2030. Therapies remain ineffective, thus developing and testing novel treatments is important for both oncologists and researchers.

Areas covered: After describing mesothelioma and the shortcomings of current therapies, the article discusses numerous therapies in turn such as immunotherapy (passive and active), gene therapy (such as suicide gene therapy) and targeted therapy such as tyrosine kinase inhibitors. The bases for different therapies and clinical trials at different phases are also described. The article concludes by detailing possible reasons for therapy failure.

Expert opinion: Despite the many attempts to uncover new therapeutic options, mesothelioma is still an orphan disease, complicated by factors such as the inflammatory microenvironment and low mutational load. Our opinion is that uncovering the biological mechanisms behind mesothelioma development will assist therapy development. The lack of efficacy of tyrosine kinase inhibitors and modest anti-angiogenic activity indicates a less relevant role for tumor cell proliferation and neoangiogenesis, thus the shortcut of treating mesothelioma with therapies from other cancers may be unsound. Conversely, many lines of evidence indicate that focussing on the survival mechanisms that tumor cells exploit may yield better therapeutics, particularly nutrition and cellular machinery.

KEYWORDS:

• Mesothelioma
• immunotherapy
• targeted therapy
• prospective therapies

Article highlights

• Current treatments for mesothelioma do not significantly enhance survival

• Despite the application of immunotherapy in melanoma treatment, challenges remain for this therapy to be effective for mesothelioma

• The use of targeted therapy may lead to improved clinical outcomes, however the presence of protein overexpression and use of inhibitors does not always follow through at the clinical level

• Although neoangiogenesis and VEGF expression are undoubtedly a feature of mesothelioma, anti-VEGF/R treatments do not appear to have a clinical benefit, excepting triple combination therapy with cisplatin and pemetrexed which extends survival by 2.7 months

• Improved understanding of the basic mechanisms mesothelioma cells use to survive in their hostile environment (with particular attention on nutrition and cellular machinery) could lead to new development pipelines and therapeutic possibilities

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded