Researchers at Hyogo College of Medicine in Japan recently reviewed the therapeutic agents suitable for the treatment of malignant pleural mesothelioma (MPM) and propose that an anti-CD26 monoclonal antibody and Flivas (naftopidil) look promising and are worth testing.
MPM is a rare and aggressive cancer affecting the protective lining of internal organs, especially the lungs and internal chest wall. This form of cancer is linked to lengthy exposure to asbestos, and usually developing decades later.
Mesothelioma’s prognosis is relatively poor, and current primary treatments are based on surgery, chemotherapy, and radiotherapy, which benefit only a small percentage of patients.
Chemotherapy drugs such as Alimta (pemetrexed), Platinol (cisplatin), and combinations of both with Avastin (bevacizumab) and amatuximab (an experimental anti-mesothelin antibody) have been tested in MPM patients.
In this review, the authors propose two new therapies commonly used to treat other conditions that could be promising for the treatment of malignant mesothelioma.
The first is a humanized anti-CD26 monoclonal antibody (YS110), widely used to treat type 2 diabetes. CD26 is highly expressed in MPM cells, but barely detected in normal mesothelial cells, and so could be a promising therapeutic target.
Tests involving human MPM cells and mouse models showed tumor growth to be significantly inhibited and extended survival when YS110 was used to treat cancer.
These encouraging results moved this drug to Phase 1 clinical trials involving 33 pretreated patients. The trial demonstrated that YS110 is safe and effective in heavily pretreated CD26-positive MPM patients. As a result, a Phase 2 study of YS110 for the treatment of advanced/refractory CD26-expressing MPM was launched.
The second therapeutic agent is based on Flivas and a naftopidil analogue (HUHS1015), belonging to the α1-adrenoceptor antagonist family and widely used for treatment of cardiovascular diseases and benign prostate hyperplasia (BPH).
Flivas has recently been shown to have antitumor properties, inhibiting the formation of new blood vessels in the cell cycle. Tests in mice demonstrated that Flivas suppresses mesothelioma cell proliferation, suggesting that Flivas and HUHS1015 can be developed as effective anti-cancer agents for the treatment of MPM.
“The prognosis of patients with MPM is poor and only modestly affected by conventional treatment. New effective agents should be introduced into clinical practice to improve treatment benefit,” the authors wrote in their review. “The CD26-targeting monoclonal antibody YS110 and the α1-adrenoceptor antagonist naftopidil and its analogue have been identified to have anti-mesothelioma activity and are expected to be evaluated soon for clinical use in mesothelioma.”