Novocure is a global oncology company that developed an innovative, non-invasive cancer therapy known as Tumor Treating Fields (TTFields). This technology represents a distinct approach to cancer treatment, operating on biophysical principles rather than biochemical ones like chemotherapy or radiation. TTFields therapy uses low-intensity alternating electric fields delivered to the tumor site to physically disrupt cancer cell replication. The therapy is administered through a portable medical device, offering a localized treatment option that can be integrated into a patient’s daily life.
Understanding Tumor Treating Fields (TTFields)
Tumor Treating Fields are generated by an alternating electric current applied transdermally to the tumor region. The therapy uses a specific range of low-to-intermediate frequencies, typically between 100 and 300 kilohertz (kHz), to target rapidly dividing cells. This frequency range is effective at interfering with the internal mechanics of large cancer cells, while having a minimal effect on smaller, non-dividing healthy cells.
The physical delivery system involves transducer arrays, which are insulated patches placed directly on the patient’s skin around the tumor location. To ensure the field covers the tumor volume effectively, the device uses two orthogonal pairs of arrays that alternate the direction of the electric field every second. This shifting field direction maximizes the chance of physically impacting cancer cells, regardless of their orientation within the tumor mass.
How TTFields Disrupt Cancer Cell Division
The efficacy of TTFields relies on the biophysical properties of cancer cells during mitosis, or cell division. The electric fields exert forces on the highly polarized molecules and structures involved in replication. This physical interference primarily targets two key stages of mitosis, ultimately leading to cell death.
During metaphase, the electric fields directly interfere with the formation of the mitotic spindle apparatus, which is composed of polarized microtubules. The forces exerted by the TTFields pull on these charged components, causing the spindle to become misaligned or aberrantly formed. This disruption prevents the chromosomes from separating correctly, resulting in an arrest of the cell cycle.
A second mechanism, known as dielectrophoresis, becomes prominent as the cell prepares to divide during telophase and cytokinesis. When the cancer cell constricts into an hourglass shape, the electric field intensity concentrates at the narrow cleavage furrow. This high-intensity field physically pushes polarized macromolecules and organelles toward the furrow, causing structural failure and fragmentation of the cell. This failure of cell division triggers programmed cell death, or apoptosis.
Approved Treatments and Device Use
The TTFields therapy is delivered using a portable device, such as the Optune or Optune Gio system, designed for continuous use outside of a clinical setting. The therapy has received regulatory approval for several aggressive solid tumors, including newly diagnosed and recurrent Glioblastoma multiforme (GBM) and malignant pleural mesothelioma (MPM). It was also approved for use in metastatic non-small cell lung cancer (mNSCLC).
For patients, the therapy requires wearing four adhesive transducer arrays directly on the skin near the tumor site. For GBM patients, the head must be shaved to ensure proper contact and field delivery. The device is intended to be worn for approximately 18 hours per day to achieve a therapeutic effect.
Recent innovations, such as the Head Flexible Electrode (HFE) arrays for GBM, have focused on improving patient comfort by making the patches lighter and thinner. The device is battery-operated and can be carried in a specialized bag, providing mobility and reducing the interruption to daily routines.
Investigating New Indications and Synergies
Beyond current approved indications, Novocure is actively investigating the potential of TTFields in a variety of other solid tumors. Clinical trials are underway to test the efficacy of the therapy in cancers such as pancreatic, ovarian, and liver cancer, as well as brain metastases. The therapeutic principle suggests a broad applicability across many types of rapidly proliferating tumors.
A significant focus involves combination therapy, exploring how TTFields can enhance the effectiveness of standard cancer treatments. TTFields are already combined with chemotherapy for GBM and MPM patients. Studies have shown that combining TTFields with agents like immunotherapy (e.g., PD-1/PD-L1 inhibitors) or radiation can create a synergistic effect, potentially increasing overall survival outcomes. Recent Phase 3 trial results suggest that TTFields combined with standard chemotherapy can improve overall survival in patients with unresectable, locally advanced pancreatic cancer.