The incidence of MPM is leveling off in the United States because asbestos use has decreased since the 1970s. However, the United States still has more cases of MPM than anywhere else in the world and the incidence of MPM is increasing in other countries. Although most mesothelioma is linked to asbestos exposure, it may also be caused by radiotherapy. Furthermore, recent data suggest that erionite, a mineral that may be found in gravel roads, is associated with the disease. Genetic factors may also play a role in MPM.
There are multiple methods to treat mesothelioma. Conventional treatments for mesothelioma typically consist of surgery, chemotherapy and radiation therapy. Surgery can include any surgical procedure. Chemotherapy includes various drugs that are considered toxic because they work by killing both healthy and cancerous cells. Radiation therapy can be delivered through different methods. However, despite aggressive treatments through surgery, chemotherapy and radiation therapy, the disease carries a poor prognosis. There are a number of new and alternative treatment options to treat malignant mesothelioma. Some of the latest mesothelioma treatment options are immunotherapy, photodynamic therapy, gene therapy and multimodality therapy.
Immunotherapy
The role of the immune system in mesothelioma is vast. Immunotherapy tries to modulate the immune system to strengthen the antitumor effect, which is hampered by defense mechanisms from the tumor. There are some genes that seem to be the key players in this process and undoubtedly further research will eventually unravel this complex interplay of cells and reveal more cell types and/or subtypes. Targeting these defense mechanisms could be the key to fully unleash the potential of immunotherapy. Since several cell types are responsible for tumor survival, combination therapy targeting multiple cell types will probably be necessary. Immunotherapy has been established in several tumor types as a proven therapy in recent years and that many trials are ongoing with promising results. In mesothelioma, the first steps have been made, and with accumulating knowledge, immunotherapy will hopefully prove to be an effective treatment.
Photodynamic Therapy
Radical pleurectomy is an operation that can be used to achieve macroscopic complete resection and when combined with intraoperative photodynamic therapy (PDT), can be performed with very low mortality and acceptable morbidity. PDT did not appear to have a positive impact on local control but may play a role in extending survival for a duration well beyond that which would commonly be expected for recurrence after surgical resection in this cohort of patients. This particular combination of treatments yielded an unexpectedly long survival for patients with advanced-stage epithelial subtype disease, the majority with N2 disease. It appeared to have little impact against, and is not recommended for, patients with nonepithelial histologic subtypes. This lung-sparing approach to mesothelioma is promising and warrants further investigation.
Gene Therapy
Gene therapy is the alteration of genetic material on the cellular level to affect how cancer cells behave. Viruses that have been altered so they do not cause disease are typically used as ‘carriers’ for the new genetic material. Some gene therapy is aimed at triggering the natural process of cellular death. Other types of gene therapy affect the ability of cells to replicate, which is how cancer spreads. Still other types are aimed at altering genes in a way that makes the cancer cells more susceptible to anti-cancer drugs. The results of a promising study show that a sufficient and beneficial oncolytic effect on malignant mesothelioma cells is obtained with adenovirus vectors Ad5/MKp-E1 and Ad5F35/MKp-E1. These adenovirus vectors could be developed as a promising gene therapy option for malignant mesothelioma.
Multimodality therapy
A multimodal approach with surgery followed by adjuvant radiotherapy has been explored. Extrapleural pneumonectomy (EPP) allows higher doses of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity with the result being a significant reduction of loco-regional relapses. However, extrathoracic metastasis remains major problem. The success of surgical resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the impetus for several groups to apply this strategy in MPM, aiming at reducing the incidence of distant relapse after surgery. Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3–4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival.
In conclusion, the prognosis for those diagnosed with pleural mesothelioma is not good. Many patients die within six months of diagnosis, some last up to a year, but few survive much beyond that. Clinical trials are constantly being undertaken in the hopes that a cure for the disease or a way to further prolong the life of a malignant pleural mesothelioma patient will be discovered.
SOURCES
Ettinger D, Akerley W, Borghaei H et al. Malignant Pleural Mesothelioma. J Natl Compr Canc Netw. 2012;10:26-41.
Cornelissen R, Heuvers ME, Maat AP et al. New roads open up for implementing immunotherapy in mesothelioma. Clinical and Developmental Immunology. 2012;2012:1-13.
Friedberg J, Culligan M, Mick R et al. Radical Pleurectomy and Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma. The Annals of Thoracic Surgery. 2012;93(5):1658-1667.
Gotoh A, Kanno T, Nagaya H, Nakano T, Tabata C, Fukuoka K. Gene Therapy Using Adenovirus Against Malignant Mesothelioma. Anticancer Res. 2012;32(9):3743-3747.
Pasello G, Ceresoli GL, Favaretto. An overview of neoadjuvant chemotherapy in
the multimodality treatment of malignant pleural mesothelioma. Cancer Treat Rev. 2012;3:1-3
the latest developments in the treatment of mesothelioma
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