New Approach to Predict Mesothelioma Drug Response

In the ongoing worldwide effort to find better treatments for mesothelioma cancer, a group of Italian doctors believe they have a better way of determining which patients will respond to a cancer medication called Gefitinib.

A cell protein called Epidermal Growth Factor Receptor (EGFR) tyrosine kinase is overexpressed in the cells of certain types of cancers, including mesothelioma.  EGFR overexpression can cause uncontrolled cell replication and faster tumor growth.  As an effective EGRF inhibitor, Gefitinib can sometimes help stop that uncontrolled growth.   But the treatment doesn’t work as well in all patients.

In a study published in the Public Library of Science, the Italian researchers say the presence of estrogen and estrogen receptors may help determine which mesothelioma patients need Gefitinib most.  Their research found that estrogen receptor beta expression appears to limit EGFR activation inside cells the way Gefitinib does.  Because EGFR is already being modulated by the presence of estrogen and estrogen receptors in some patient’s cells, giving them Gefitinib too is unlikely to have a significant impact for them.

To test the theory, the researchers limited estrogen receptor beta expression in certain mesothelioma cells in the lab.  The result was a more invasive cancer subtype, a greater likelihood that the cells could spread and start new tumors, and elevated EGFR-triggered growth.  Re-introducing estrogen receptor beta had the opposite effect on cells.

The research is important because identifying the most effective medications as early as possible can have a dramatic effect for mesothelioma patients.  Mesothelioma, which is caused by exposure to asbestos, can be extremely fast-growing.  If doctors can use simple blood tests to help target patient treatments, they may waste less time trying and failing with various other medications.

The authors concluded that understanding the role of estrogen receptor beta expression in EGFR activation “provides a rationale to facilitate the targeting of a subgroup of mesothelioma patients who would benefit most from therapy with Gefitinib alone or in combination with Akt inhibitors.”

Sources:

Pinton, G et al, “Estrogen Receptor Beta Exerts Tumor Repressive Functions in Human Malignant Pleural Mesothelioma via EGFR Inactivation and Affects Response to Gefitinib”, Nov 29, 2010, Public Library of Science One (PLoS One), 5(11): e14110.
Govindan,R et al, “Gefitinib in Patients with Malignant Mesothelioma: A Phase II Study by the Cancer and Leukemia Group B”, Nov 22, 2004. Clinical Cancer Research.