Gene Therapy Drug Controls Growth of Mesothelioma

Update: This post was updated May 17, 2022, with data from Memorial Sloan Kettering Cancer Center about the phase 2 trial for the mesothelioma gene therapy.

The ultimate goal of mesothelioma research is to find a cure. That accomplishment could be years away, and the hope until then is to find a way to manage this cancer.

A few researchers might have a treatment with the potential to keep mesothelioma from growing and spreading.

A phase 2 trial involving tazemetostat was for people with a relapsed or stubborn pleural mesothelioma. Tazemetostat, a type of targeted cancer therapy, inhibits the gene “enhancer of zeste-homolog 2 (EZH2).” This gene is overexpressed in mesothelioma tumors and aids the cancer cells’ proliferation.

While the gene therapy didn’t lead to a complete disease response, it did help stop mesothelioma’s growth in many cases.

 

How Tazemetostat Works for Mesothelioma Treatment

EZH2 is connected to the mutation of BAP1, which is another gene. BAP1 suppresses tumor activity, and its inactivation is one less defender against cancer. Around 50% of pleural mesothelioma cases have mutations of BAP1.

The mutation of BAP1 leads to EZH2’s overexpression. Tazemetostat doesn’t solve the BAP1-loss problem, but it does block EZH2.

The study’s research team included mesothelioma researcher Dr. Marjorie Zauderer, who is Co-Director of the Mesothelioma Program at Memorial Sloan Kettering Cancer Center. She is especially interested in studying BAP1 gene mutations in pleural mesothelioma.

“This is the first targeted therapy we’ve seen to have a real effect on slowing or stopping pleural mesothelioma,” Dr. Zauderer said on the Memorial Sloan Kettering website. “Although targeted therapies have been successful with many other cancers, one problem with mesothelioma has been that there aren’t many alterations we can target. Now that is changing.”

There were 74 participants in the study at Memorial Sloan Kettering Cancer Center. Of them, 70 (95%) were confirmed to be BAP1-deficient and thus likely had high levels of EZH2. A few of the notable data points in the results are below:

• Around 51% of patients had a controlled disease — meaning it hadn’t progressed — after 12 weeks.
• Two patients had a partial response, and 33 had a stable (stagnant) disease after 12 weeks.
• A total of 47 patients (64%) achieved some level of response.

The researchers were pleased with the results. They wrote that the disease control rate and number of stable disease cases “showed antitumor activity” in BAP1-mutated cases.

“After we found out how common BAP1 was in mesothelioma, I took action to make sure every mesothelioma case at MSK was tested for the mutation,” Dr. Zauderer said. “That way, when a drug like tazemetostat becomes available for testing, we have already identified who may benefit. All this testing — genetic, molecular, and other types of profiling — yields information that can prove useful if a new treatment pops up.”

 

Hope for Emerging Mesothelioma Treatment Options

Gene therapy is one of many emerging methods that may find a mesothelioma cure. Others are immunotherapy, virotherapy and photodynamic therapy.

Our staff can help explain some of these treatment methods in more depth. We also can help you find cancer centers exploring these options in studies.

Additionally, if you’d like to find a surgeon or specialist for standard treatment, we can assist you. Email our patient advocate and registered nurse, Karen Ritter, at karen@mesotheliomaguide.com for more help.