Researchers Pinpoint Optimal Frequency Using TTFields for Mesothelioma Treatment

The makers of TTFields for mesothelioma treatment have released a new report that sheds light on how the therapy can be most effective. 

TTFields stands for “Tumor Treating Fields”. It is a device that emits intermediate frequency alternating electrical fields. These fields are designed to disrupt cancer DNA and shrink tumors. 

The FDA approved TTFields for mesothelioma treatment in 2019. At the time, it was the first new treatment for this intractable cancer since 2004. It is still the only non-invasive treatment for pleural mesothelioma. 

The new report from researchers at Novocure may help doctors use TTFields more effectively for their patients with inoperable mesothelioma.

TTFields for Mesothelioma Treatment

The Tumor Treating Fields approach was first used to treat glioblastoma. This is a hard-to-treat and fast-growing type of brain tumor. Research showed that TTFields could slow the growth and even shrink some glioblastoma tumors. 

Pleural mesothelioma is also fast-growing and difficult to treat. Malignant mesothelioma rarely responds to standard cancer treatments alone. Chemotherapy with pemetrexed and cisplatin is the standard of care. But even chemotherapy usually only extends life a few months. If a patient is not eligible for mesothelioma surgery, there are few good options. 

TTFIelds for mesothelioma treatment is a vest-like device that patients wear against their chest. The alternating electrical fields disrupt the DNA inside mesothelioma cells. Damaged cancer cells are not able to grow, replicate, and spread.  When paired with chemotherapy, the device is even more effective at fighting mesothelioma. 

Doctors know that TTFields for mesothelioma treatment can help patients. But they do not yet fully understand how it works. The Novocure researchers dug deeper to show the mechanism behind the system and to find the frequency that is most damaging to mesothelioma tumors. 

DNA Disrupter Impacts Proteins

Proteins dictate the life cycle and day-to-day operations of all cells, including mesothelioma cells. Proteins allow mesothelioma cells to “communicate” with the rest of the body and get their needs met. Proteins also help repair damage. A cell’s DNA determines how much of these proteins the cell expresses.

TTFields for mesothelioma treatment scrambles the DNA. The Novocure researchers say the damaged DNA produces too much of some proteins and not enough of others. If the cells are exposed to toxic chemotherapy drugs, they do not have access to the proteins they need for repair. TTFields can also trigger the production of proteins that cause early cell death.  

“Efficacy of TTFields for the treatment of MPM is associated with increased DNA damage, elevated levels of DNA-damage related cell cycle arrest proteins, and reduced expression of FA [repairing] pathway proteins,” writes lead author Helena Mumblat in The International Journal of Radiation Oncology, Biology, Physics.

The team tested different combinations of pemetrexed, cisplatin and TTFields on mesothelioma cell lines in the lab. They found that 150 kHz is the most damaging frequency of TTFields for mesothelioma treatment.

TTFields is marketed under the brand name Optune Lua. It is approved in combination with chemotherapy for mesothelioma patients who are not candidates for surgery. Tests show the treatment can improve median overall survival.

Source:

Mumblat, H, et al, “Impact of Tumor Treating Fields (TTFields) on DNA Damage Repair in Mesothelioma”, November 1, 2021, International Journal of Radiation Oncology, Biology, Physics, Volume 111, Issue 3 Supplement, https://www.redjournal.org/article/S0360-3016(21)02167-2/fulltext#%20