Targeting Estrogen Receptor Boosts Effectiveness of Mesothelioma Chemotherapy

Malignant mesothelioma is caused by exposure to asbestos and is notoriously hard to treat.  The chemotherapy combination of cisplatin and pemetrexed is standard of care (SOC) for treating pleural mesothelioma, even though only 40% of patients respond to this therapy. Chemotherapy does not typically extend life by more than a few months and the median overall survival for mesothelioma is between 9 and 17 months.

But pharmaceutical researchers at the University of Piemonte Orientale “A. Avogadro” in Italy and the department of biosciences and nutrition at the Karolinska Institute in Sweden say they may have found a way to bolster the effectiveness of chemotherapy for mesothelioma. The focus of their study was Estrogen Receptor Beta (ERbeta), an estrogen sensitive molecule in the nuclei of cells that helps suppress the growth of tumors.

Dr. Giulia Pinton and her colleagues treated human mesothelioma cells with the ERbeta agonist KB9520 with promising results. First, the molecule showed “significant anti-proliferative effect” in the mesothelioma cells, preventing them from replicating and growing so quickly. Second, activating the ERbeta in mesothelioma cells with KB9520 sensitized the cells to treatment with cisplatin, enhancing the tumor inhibiting effects and increasing apoptosis (cell death).

Even more encouraging, when the team gave KB9520 along with cisplatin and pemetrexed to mice with mesothelioma tumors, the growth of those tumors was “significantly inhibited”. Not only did the drug combination slow down the growth of tumors, but it even appeared to help protect healthy cells from the damaging effects of cisplatin. Damage to the non-malignant cells accounts for most serious side effects in patients undergoing chemotherapy.

“Thus, combination of KB9520 with SOC (cisplatin/pemetrexed combination) may increase the sensitivity of malignant pleural mesothelioma tumors to the SOC regimen in patients and perhaps result in higher response rates, extended progression free survival, and prolonged overall survival, without adding toxicity,” concludes the report in Molecular Cancer.

Although numbers are gradually declining as asbestos regulations have taken effect, an estimated 2,500 people die of mesothelioma in the U.S. each year.

Source:

Pinton, G et al, “Agonist activation of estrogen receptor beta (ERbeta) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity”, October 2014, Epub ahead of print