Researchers in Spain are developing what they hope will be a more effective sarcomatoid mesothelioma treatment. The new treatment focuses on a pair of drugs that are already being tested in humans.
Mesothelioma impacts about 2,500 Americans each year. Sarcomatoid mesothelioma is a rare form of this rare cancer. About a quarter of the annual cases are sarcomatoid.
This form of cancer is even more aggressive than epithelioid mesothelioma. But sarcomatoid mesothelioma treatment is not significantly different. Neither are the results.
Chemotherapy is the Primary Sarcomatoid Mesothelioma Treatment
Most people with malignant mesothelioma receive chemotherapy with cisplatin and Alimta. This is the usual first-line treatment. This treatment works for fewer than half of patients. In these patients, it may extend life for only a few months.
Whether patients receive epithelioid, biphasic, or sarcomatoid mesothelioma treatment with chemotherapy, the outcomes are often the same. Few mesothelioma patients live beyond 18 months.
Chemotherapy poisons mesothelioma cells to keep them from proliferating. But the Spanish doctors propose a new way to treat the sarcomatoid form of mesothelioma. Their approach focuses on molecular targets.
Accidental Discovery of New Approach
Discovery of the potential new sarcomatoid mesothelioma treatment started by accident.
Researchers investigating bladder cancer in mice deleted expression of two tumor-suppressing genes. But instead of causing bladder cancer, they ended up triggering sarcomatoid mesothelioma.
Without these genes, genetic pathways called MEK/ERK and PI3K kicked into high gear. The scientists say these pathways allowed sarcomatoid mesothelioma to grow and spread easily.
This was an important insight into the molecular mechanisms behind sarcomatoid mesothelioma treatment. The next step was to find drugs that would block these tumor-promoting pathways.
Testing New Drugs for Mesothelioma
The MEK/ERK and PI3K pathways play a role in several types of cancer. As a result, drugs have already been developed to block them. Selumetinib is a MEK inhibitor and AZD8186 targets PI3K.
“We chose drugs that were already being tested for other human tumours, because their toxicity is well understood and so they can be used in clinical trials soon,” says study author Paco Real. Dr. Real is with the Molecular Oncology Programme at Spain’s National Center for the Study of Cancer (CNIO).
Clinical trials are the next step for the proposed sarcomatoid mesothelioma treatment combination. Dr. Real and his colleagues hope to start recruiting mesothelioma patients soon.
Marques, M, et al, “Combined MEK and PI3K/p110b inhibition as a novel targeted therapy for malignant mesothelioma displaying sarcomatoid features”, January 7, 2020, Cancer Research, Epub ahead of print, https://cancerres.aacrjournals.org/content/early/2020/01/04/0008-5472.CAN-19-1633
“Cancer Research. Two drugs used in combination prove to be effective against most aggressive asbestos cancer in mice”, News Release, CNIO website, https://www.cnio.es/en/news/publications/drugs-in-combination-malignant-mesothelioma-asbestos-exposure/