Study Uncovers Drug Combination for Sarcomatoid Mesothelioma
Researchers in Spain have discovered a drug combination showing potential in treating the most difficult-to-treat type of malignant mesothelioma.
Selumetinib and AZD8186, already being studied separately in clinical trials for other cancers, displayed efficacy when used in combination on mesothelioma of the sarcomatoid cell type.
Researchers at the Spanish National Cancer Research Centre made the discovery during their study using mice models and human tumor cells in the laboratory.
“The findings, we hope, are relevant,” Dr. Paco Real, who led the study, told The Mesothelioma Center at Asbestos.com. “We don’t know yet how important they are. We’re still being cautious in our predictions. Curing mice is different than curing patients.”
Cancer Research published the findings Jan. 7.
Pushing for Clinical Trial Help
Real wants to begin a clinical trial with human patients as soon as possible, but he still needs one of the major drug companies to participate.
“The most important thing now is persuading the pharmaceutical industry to support a clinical trial,” he said. “We’re pushing hard in that direction. We’ve done all we can do to reach this point. Without a pharmaceutical company willing to help, though, we’re wasting our time.”
Although costs of clinical trials are often minimal for patients, it costs hundreds of thousands of dollars — even for the beginning phases of drug development — to reach eventual governmental approval.
The rarity of mesothelioma makes clinical research funding difficult, particularly when studying the rarest of the three cell types.
Sarcomatoid accounts for an estimated 15% to 20% percent of patients. It also is the toughest type to treat.
Patients typically live only six months after a diagnosis with mostly palliative therapy available.
The more common, more treatable, cell types are epithelioid and biphasic.
“This type of mesothelioma has not been widely studied, and has a poor prognosis with no targeted therapy,” Real said. “This combination [of drugs] makes sense, though. The findings were not exceptionally surprising, or completely outside the box.”
Pivoting from Bladder Cancer to Mesothelioma
Researchers originally were testing the drug combination for bladder cancer while focusing on two particular tumor suppressor genes and how they were being inactivated.
A mid-study switch, though, drew them to the even more aggressive sarcomatoid mesothelioma.
They discovered the drugs in combination reduced the proliferative and invasive capacities of mesothelioma by targeting similar molecular pathways.
Doctors are using Selumetinib, which is licensed to AstraZeneca, in clinical trials involving certain non-small cell lung cancers and thyroid cancer.
The U.S. Food and Drug Administration in 2019 granted Breakthrough Therapy Designation for Selumetinib’s use with a rare and incurable genetic condition found in young children.
AZD8186 also is being studied in numerous clinical trials involving certain types of prostate, breast and non-small cell lung cancers.
“We found a drug combination that was effective in both mice and human cell lines,” Real said. “We chose drugs that already were being tested for other tumors, so their toxicity is well understood. These are two compounds that are by no means new. They can be used in clinical trials soon.”
The research also identified specific molecular markers on the tumor cells for predictive therapy response, which could be used for clinical trial patient selection.
“At this point, it’s impossible to predict exactly how important our findings are,” he said. “It depends on the benefit the patients will see. We know we can increase the lifespan of a mouse. We need a clinical trial to see where it goes now. Hopefully, the impact will be significant.”