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
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
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
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.
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 antiumour agent with a good preliminary pharmacokinetic, toxicity and safety data for the treatment of malignant mesothelioma. Activities included at BERMES project (Novel BERberine derivative for Malignant MESothelioma) are expected to close the translational gap by pulling the product up to the clinical development