Biomarker May Predict Chemotherapy Response in Mesothelioma

Cancer researchers in Japan say they may have found a way to help predict which mesothelioma patients are most likely to respond well to treatment with Alimta.

Alimta (pemetrexed) was FDA approved in 2004 for the treatment of mesothelioma, a virulent form of lung cancer linked to asbestos exposure. Alimta is often administered along with the platinum-based drug cisplatin, although this first-line mesothelioma treatment combination has been shown to have only limited success.

Part of the problem is that it is difficult to predict which mesothelioma patients will respond to which types of therapies. Mesothelioma treatment, therefore, often involves a process of trial and error to find the therapy that works best. Unfortunately, this approach can cost patients valuable time while their fast-growing mesothelioma tumors continue to progress.

But doctors in the Department of Pulmonary Medicine and Oncology at the Nippon Medical School in Tokyo say the structural glycoprotein osteopontin may be a predictor of Alimta sensitivity. The team tested Alimta in six malignant pleural mesothelioma cell lines and found that three of them were sensitive to the drug. Gene expression profiling was then performed on each of the cell lines to identify genes that might be associated with that sensitivity.

“Pathway analysis revealed that osteopontin was an important target in pemetrexed (Alimta) sensitivity,” writes lead author Susumu Takeuchi in the International Journal of Oncology. “Overexpression of osteopontin was observed in the sensitive cells by quantitative PCR and western blot analysis.”

According to Takeuchi and his team, Alimta’s effectiveness against mesothelioma tumors is directly related to the overexpression of osteopontin. Two of the patients whose mesothelioma tumors were reduced in size with Alimta-based chemotherapy were found to have high osteopontin expression. The team concludes that the glycoprotein “may be used as a single predictive biomarker” of the effectiveness of Alimta treatment and can be used to help in treatment planning.

Mesothelioma is a rare and difficult-to-treat cancer caused by exposure to asbestos. Alimta was the first and only drug approved specifically to target malignant pleural mesothelioma cancer cells. Now commonly used in combination with cisplatin or another chemotherapy medicine, Alimta helps doctors manage mesothelioma by blocking the action of a cellular chemical that helps cells to multiply. It belongs to a group of chemotherapy drugs known as antimetabolites.

Source: Takeuchi, S et al, “Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed”, April 7, 2014, International Journal of Oncology, Epub ahead of print