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Posted on Friday, Feb 12, 2010

New Treatments for Mesothelioma Target Tumor Growth Factors

Successful treatment of malignant pleural mesothelioma remains elusive for doctors, scientists, and researchers alike, leaving the prognosis for mesothelioma patients poor with a median survival of less than two years. Mesothelioma has proven to be chemoresistant, rendering many of the current chemotherapy treatments inadequate. According to an article published in the journal Current Drug Targets, however, now is the time to introduce new biologic drugs that target tumor growth factors.

The growth factors or proteins which promote malignant cell growth ultimately supplying blood and oxygen to the growing tumor, include vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), and insulin-like growth factor (IGF). The authors of the report found that in many cases the growth factors appeared higher in malignant mesothelioma patients than in control subjects or in healthy individuals. This indicates that using the biomarkers for diagnosis, prognosis, and therapy is promising.

Biologic drugs are made from a living organism, as opposed to chemicals, and have added major therapeutic options for the treatment of many diseases. The resistance of mesothelioma is due to its apoptotic defect, which prevents the medicines from killing the cancer cells, and new biologic drugs such as vorinostat, bortezomib, everolimus and temsirolimus, have proven effective in some early clinical trials targeting the growth factors.

Vorinostat, currently used to treat cutaneous T-cell lymphoma (CTCL), a blood cancer, is being studied as a new treatment for many solid malignancies. Now in a phase III trial with advanced, previously treated pleural mesothelioma patients this drug has shown to increase aptopsis induced by the combination of cisplatin and pemetrexed. These results make this a valid option for improving the response to standard chemotherapy treatments.

Similar results were found with bortezomib. Approved by the FDA for multiple myeloma treatment, bortezomib has proven effective fighting activation of nuclear factor kB, which regulates proteins that evade apoptosis. Results were positive in mesothelioma patients for bortezomib as both a single agent as well as when administered prior to the combination of cisplatin and pemetrexed. Trials are ongoing for this and other protein inhibitor agents.

Many other biologic agent clinical trials are underway for drugs targeting malignant pleural mesothelioma. Other drugs being tested include: bevacizumab, carboplatin, dasatinib, sunitinib, sorafenib. The researchers hope that the studies result in valid therapeutic options for chemorefractory patients.

“Targeted treatments represent a hot field” as mesothelioma researchers now focus on therapies targeting tumor growth factors. The targeted interventions against mesothelioma may offer new therapeutic options for patients in the future.