Mesothelioma

Malignant mesothelioma is a rare, aggressive and highly resilient malignancy that occurs in the thin layer of tissue known as mesothelium, that covers most internal organs like the lungs, the peritoneal cavity, the heart and even, the testis.

Malignant Pleural Mesothelioma is the most common type accounting about 80% of the cases. About 3,200 new cases of pleural mesothelioma are diagnosed in the US annually. In European Union, according to data extracted from the European Cancer Incidence and Mortality database (EUROCIM), only the incidence of pleural mesothelioma is about 20 cases per million habitants with a large inter-country variation. 

An asbestos-related cancer

All forms of mesothelioma are caused primarily by the inhalation of asbestos fibres being most commonly diagnosed in individuals who worked with the mineral in an industrial setting.  

When microscopic asbestos fibers are inhaled, the lodge in the pleura, the abdomen or the heart surrounding tissue. After many years, these fibers can cause genetic changes that create cancer cells.

Incidence & latency period

Mesothelioma represents less than 1% of all cancers. However, its burden is raising at an annual growth rate of 4.5% and with a mortality rate of 4.9 per million people (about 107,000 deaths yearly at the 1994-2008 period).

In European Union countries, asbestos was finally banned by January 2005. However, since the median latency period between asbestos exposure and disease onset is 44.6 years, an incidence peak is expected beyond 2020 in most EU countries. Thus, there will be still the urgent need for an improved treatment over the next decades.

Treatment

With a natural history of seven to nine months if untreated and less than 5% of five-year survivors, there is wide room for therapeutic improvement. The current trimodality treatment for early stage disease with surgery, chemotherapy and radiation is potentially curative. Unfortunately most patients (90%) either are too ill to undergo aggressive surgery or are diagnosed with advanced disease, where chemotherapy remains the most common therapy option.

The standard first line treatment is the combination of pemetrexed and cisplatin, that has limited efficacy and comes with harsh side-effects. The insights into the complex biology of the tumour over the last ten years, has rendered novel druggable targets and several clinical trials have been run with existing and newer targeted drugs. However, only modest improvements in the treatment have been achieved.  Immunotherapies that have revolution the cancer therapy, represents a new hope, although have not shown yet sufficient benefit on overall survival as monotherapy and are currently being developed in combination with the standard of care. The search for an improved treatment or cure is still open.

NAX035 an innovative berberine derivative has exhibited efficacy as antitumour agent with a good preliminary pharmacokinetic, toxicity and safety data when administered as oral therapy for the treatment of malignant mesothelioma.  Activities of BERMES (BERberine derivative for MESothelioma treatment are expected to close the translational gap (death valley) by pulling the product up to the clinical development.