TTFields and chemotherapy offer one of the most potent combinations against malignant mesothelioma tumors. Now a new study reveals why they work so well together.
Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. They are delivered into the chest of mesothelioma patients with a vest-like device marketed under the brand name Optune Lua.
In 2019, a combination of TTFields and chemotherapy became the first new FDA-approved treatment for mesothelioma in 15 years.
Now, a new report in the journal Lung Cancer sheds light on the synergy between the two modes of mesothelioma treatment.
Combating Cancer with Electrical Currents
The Tumor Treating Fields approach was created by Jersey-based Novocure. The technology uses electrical fields to destabilize critical proteins responsible for cell division. When these proteins cannot do their job, cancer cells cannot divide. TTFields were first used to treat deadly glioblastoma brain tumors.
Like glioblastoma, malignant mesothelioma grows fast and is very hard to treat. A clinical trial called STELLAR tested TTFields and chemotherapy on 80 mesothelioma patients. The study showed that the combination is a viable option for people with few alternatives.
Patients in the STELLAR trial had a median overall survival of more than a year-and-a-half. That is six months longer than patients who only had mesothelioma chemotherapy.
In all, 97 percent of mesothelioma patients who received TTFields and chemotherapy had some amount of disease control.
The Synergy of TTFields and Chemotherapy
Scientists know that TTFields and chemotherapy work together. The goal of the new study was to determine exactly how.
The new report comes from Novocure researchers in Israel and Germany. They first treated two mesothelioma cell lines with TTFields to see what dose did the most DNA damage. Then they exposed the cells to both TTFields and chemotherapy. They also used the combination on mesothelioma tumors in live mice.
The researchers discovered that TTFields reduced expression of certain proteins responsible for repairing DNA damage. Specifically, these proteins are responsible for repairing DNA damage caused by the chemotherapy drug cisplatin.
“This research demonstrated that the efficacy of TTFields for the treatment of MPM is associated with reduced expression of FA-BRCA pathway proteins and increased DNA damage,” writes lead author Helena Mumblat. “This mechanism of action is consistent with the observed synergism for TTFields-cisplatin…as cisplatin-induced DNA damage is repaired via the FA-BRCA pathway.”
TTFields and chemotherapy is approved for mesothelioma patients who have advanced disease and are not candidates for surgery. Mesothelioma patients with implanted devices like pacemakers or defibrillators are not eligible for this treatment. Only providers who are trained and certified by Novocure can offer it.
Mumblat, H, et al, “Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models”, August 27, 2021, Lung Cancer, Online ahead of print, https://linkinghub.elsevier.com/retrieve/pii/S0169500221005122
“FDA Approves the NovoTTF-100L™ System in Combination with Chemotherapy for the Treatment of Malignant Pleural Mesothelioma”, May 23, 2019, News Release, Novocure Website, https://www.novocure.com/fda-approves-the-novottf-100ltm-system-in-combination-with-chemotherapy-for-the-treatment-of-malignant-pleural-mesothelioma/