Cancer cells divide and multiply rapidly within the cancer tumor. These cancer cells carry different types of electrically charged elements that play a role during the cell division process. Other healthy cells in the abdominal region multiply at a much slower rate, if at all, and/or have other different properties such as a different size, compared to the cancer cells. Thus, normal cells rarely include the same electric properties as the dividing cancer cells and are not expected to be affected by TTFields.

TTFields Mechanism of Action

The NovoTTF-100L(O) device used in this study delivers very low intensity, alternating electric fields to the tumor site through the skin and other more superficial tissues. These fields are known as Tumor Treating Fields or TTFields. Preclinical studies showed that due to the shape and size of cancer cells when they are multiplying, TTFields cause electrically-charged cellular components of these cells to change their location within the dividing cell, which can disrupt their normal function and may ultimately lead to cell death. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields interfere with the normal orientation of these tiny motors since they are electrically-charged as well. As a result of these two effects, tumor cell division is slowed, and may result in cellular death or cell division reversal, leading to inhibition of tumor growth after continuous exposure to TTFields. Preliminary data also indicate that the TTFields may affect the healthy tissue cells within the abdominal region much less than cancer cells since healthy tissue cells multiply at a much slower rate, if at all.

A summary of TTFields’ mechanism of action is illustrated in the following animation:


[Science of TTFields Video]

Past Clinical Experience

A number of systems developed to deliver TTFields to different tumors have been tested to date. The main difference between the previously tested systems and the NovoTTF-100L(O) is the frequency of TTFields provided by each system. The frequency is adjusted by the manufacturer of the systems in order to optimize the treatment for each treated cancer, based on data from laboratory experiments.

The NovoTTF-100L(O) has been already tested in a pilot study (similar to a phase 2/safety study) for 31 patients with recurrent ovarian cancer in combination with paclitaxel to test the safety and preliminary efficacy of TTFields in this indication. The result of this study were the basis for the design of the ENGOT-ov50/INNOVATE-3 study.

Another system delivering TTFields (200 kHz), called Optune®, has been approved for the treatment of recurrent and newly diagnosed glioblastoma (a type of brain cancer) by the Food and Drug Administration (FDA) in the United States under the Premarket Authorization (PMA) pathway and has obtained a CE mark in Europe for the same indications.  In 2019, TTFields were approved by the FDA as Optune Lua (formerly NovoTTF-100L) for malignant pleural mesothelioma (MPM), in combination with chemotherapy, under the HumanitarianDevice Exemption (HDE) pathway. In 2020, NovoTTF-100L received CE marking in Europe for MPM.


Side Effects

Based on the science behind TTFields and the clinical results to date, the NovoTTF-100L(O) is not expected to have systemic side effects in patients suffering from ovarian cancer. In previous studies performed with Optune®, the system tested in glioblastoma, a high percentage of patients have experienced local skin irritation beneath the transducer arrays which was mild to moderate in severity in the vast majority of cases.

In the aforementioned study for ovarian cancer, there were no serious side effects attributed by the study doctors to TTFields. The only side effect which was related to the device was skin irritation under the transducer arrays placed on the skin which in the majority of the cases was mild to moderate in severity.

The information provided in this website is partial, and you should consult with your treating doctor concerning the complete safety profile of TTFields.

Please note that while the adverse event information from the other clinical studies may be relevant to use of the device for ovarian cancer, it is not necessarily specific to your condition, and the aforementioned study for ovarian cancer included a small number of patients. Therefore, the safety profile of the device for ovarian cancer has not been established and may be different.