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a profoundly
different
approach to cancer
treatment

Novocure’s Director of Preclinical Research, Moshe Giladi, joined the company in August 2005. Dr. Giladi’s team in Israel researches the mechanism of action and the biological application of alternating electric fields.

For over 15 years, Novocure’s researchers have explored a different approach to cancer treatment that puts the patient first.

Medical advancements have led to dramatic improvements in cancer survival in the last 50 years. In the United States, five-year survival for all cancers rose from 49 percent in the 1970s to 69 percent in this decade.

Despite meaningful advancements in cancer treatment, we believe a significant unmet need to improve survival and quality of life remains. Of the 22,280 women diagnosed with ovarian cancer in the U.S. each year, only 46.2 percent live past five years. Of the 224,390 Americans diagnosed with lung cancer annually, only 17.7 percent are alive five years later. Of the 53,070 people diagnosed with pancreatic cancer in the U.S. each year, only 7.7 percent survive past the five-year mark.

For patients facing some of the most aggressive forms of cancer, these grim statistics are their reality. The five-year survival rates are simply unacceptable. We believe a profoundly different approach to cancer treatment is needed.

Innovative Breakthroughs

Novocure is developing a profoundly different cancer treatment centered on a proprietary therapy called TTFields, the use of alternating electric fields tuned to specific frequencies to disrupt solid tumor cancer cell division. The basic mechanism behind TTFields may be broadly applicable and is not limited to a specific solid tumor type or genetic marker. Importantly, we believe TTFields has the potential to increase survival when used in combination with other cancer therapies without significantly increasing side effects.

the science of novocure

a message from our chief science officer, Eilon Kirson, MD, PhD

For more than a century, advances in cancer treatment have depended upon innovative researchers and clinicians and hard-fought breakthroughs. Each step forward was sparked by an idea or a hypothesis.

Today’s traditional treatments–surgery, radiation and chemotherapy—were once thought of as radical, and each therapy evolved over time. Throughout medical history, advancements small and large led to improved survival rates and quality of care over prior treatments. Every several decades, a major breakthrough made a significant enough impact to change the course of cancer treatment for countless patients.

Yet for many people diagnosed with some of the most aggressive forms of cancer, traditional treatments aren’t enough, as is evident from low and stagnant survival rates in certain forms of cancer. In order to make a meaningful impact in the lives of these patients, we believe that we need a different approach to solid tumor cancer treatment.

In 2000, Yoram Palti, Novocure’s founder and professor emeritus of physiology and biophysics at the Technion - Israel Institute of Technology, hypothesized and began testing such an approach. Instead of searching for ways to improve upon existing cancer therapies, he employed his knowledge of physics to influence biological processes in cancer cells, particularly mitosis. Professor Palti proposed that alternating electric fields tuned to specific frequencies could disrupt cancer cell division without causing many of the life-altering side effects associated with other traditional treatments. Over a decade of preclinical and clinical research in more than 15 cancer cell lines has proven he was right.

Professor Palti viewed the problems with traditional cancer treatments through an innovative lens. He assessed the need for improved outcomes and his own knowledge in physics and biology, and questioned what people think about existing treatments and where they might be stuck in their thought patterns. By thinking of killing cancer from a new perspective, he discovered another way.

The spirit of Professor Palti’s original hypothesis remains a core pillar of Novocure today. As innovators ourselves, we carried Professor Palti’s original idea forward. Like the many innovators in cancer research who’ve come before, we see the limitations of current treatments not as a challenge, but as an opportunity to approach the problem—and find a solution—in a profoundly different way.

Eilon Kirson, MD, PhD

Chief Science Officer
and Head of Research
and Development

Advancing alternating electric field therapy

Novocure’s Chief Science Officer and Head of Research and Development Eilon Kirson, MD, PhD was one of the first employees to join the company in 2002. Dr. Kirson has global responsibility for Novocure’s preclinical and clinical and product development programs, as well as the company’s regulatory strategy.

“Even after 15+ years of research, there is still more being learned about treatment with alternating electric fields. We are excited about the promising application of this profoundly different approach to solid tumor cancer treatment, for glioblastoma and beyond.”

— Eilon Kirson, MD, PhD
Chief Science Officer and
Head of Research and Development

An Effective Anti-Mitotic Treatment

In order to understand treatment with TTFields, one must first be familiar with electric fields and how they can be utilized for medical applications. All fields exert forces on specific objects that are spatially located inside the field. For example, gravitational fields exert forces on masses, and magnetic fields exert forces on iron. Similarly, electric fields exert forces on polarized molecules and can be used across multiple medical applications at specific frequencies. Low frequency or pulsed electric fields can depolarize cell membranes, as seen in artificial pacemakers, while high frequency electric fields can generate heat, as seen in radiofrequency ablation. Intermediate frequency electric fields, long thought to have no significant biological effect, have now been shown to inhibit the growth rate of a variety of cancer cell lines and cause cancer cell death.

TTFields use low-intensity, alternating electric fields tuned to specific frequencies to disrupt the highly choreographed mitotic process essential to tumor growth. While many intracellular molecules are slightly polarized or neutral, some are highly polarized and strongly affected by intermediate-frequency, alternating electric fields. For example, tubulin is a highly polarized molecule that must orient spatially to form the mitotic spindle, which segregates chromosomes into two daughter cells during mitosis. In the presence of electric fields, tubulin aligns with the direction of the electric field, causing disruption of mitotic spindle formation and eventual cell death. Septin is another highly polarized molecule that must orient spatially to form the contractile ring needed to split daughter cells during mitosis. In the presence of electric fields, septin aligns with the direction of the electric field, leading to improper localization of the contractile ring. This process causes membrane blebbing and eventual cell death.

LOW INTENSITY ALTERNATING ELECTRIC FIELDS AND THEIR EFFECT ON MITOSIS

Alternating electric fields affect tumor cells by arresting mitosis, slowing TTFields-treated cell division time from less than one hour to more than three hours (a). Some cells in the field may also disintegrate in the later stages of cell division (b,c).

Credit: Physics Today, adapted from Kirson et al. Cancer Res. 64, 3288, 2004

making waves
in cancer care

TTFields noninvasively exert an antimitotic effect via delivery of frequency-tuned electric fields that act specifically on solid tumor cells

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TTFields impact metaphase

application of therapy

Novocure’s profoundly different approach to cancer treatment utilizes low-intensity, alternating electric fields tuned to a specific frequency with the goal of disrupting cancer cell division and tumor growth. To apply these electric fields to the body, two sets of transducer arrays are placed front to back and side to side to surround the region of treatment. The arrays are connected to an electric field generator, and the direction of the electric field oscillates rapidly between each set of arrays. The electric field penetrates the entire volume of tissue between the arrays and, at the right frequency, into the cells inside the field.

The cell membrane serves as an effective filter for electric fields unless tuned to a specific frequency, with the frequency required to penetrate the membrane principally linked to cell size. Cancer cells tend to be smaller than normal healthy cells and, as a result, the frequency of the electric field can be tuned to the specific size of the targeted tumor cell.

Electrode placement is optimized for each patient

The distribution of the field depends on the exact layout of the transducer arrays and the passive electrical properties, mainly resistance, of the different tissues between them. Array placement is optimized for each patient using proprietary software called NovoTALtm, based on morphometric measurements of the patient’s anatomy according to a recent MRI scan and the location of the tumor.

Q&A

Ze’ev Bomzon
Director of Science

Physicist Ze’ev Bomzon and his team of researchers aim to optimize the delivery of alternating electric fields to solid tumor cancers and further the understanding of the mechanism of action.

What type of research do you conduct?

We do a lot of physics research. Our main focus has been on optimizing the delivery of TTFields. We do a lot of simulation, numerical work and experimental work as well, such as measuring TTFields in various situations. We also continue our research into the mechanism of action of TTFields. That includes a lot of work with our preclinical teams and looking at things such as electric properties of cells, which are relevant to enhancing our understanding of how TTFields penetrate into the cells.

What are some of the challenges of working with a profoundly different technology?

Although Novocure has been researching TTFields for more than 15 years, that’s not a long time in the grand scheme of things. We continue to deepen our understanding of the mechanism of action of TTFields. Because our therapy is so different, it has taken time for the broader scientific community to begin researching TTFields. However, a number of institutions have started to study TTFields in the last several years.

Additional research, whether done internally or externally, will help inform our therapy and could result in better outcomes for patients.

Our technology bridges physics with biology, and we have to communicate information to people with various scientific backgrounds. The way physicists describe the world is very different from the way biologists describe the world. For many people, the concept of an electric field is abstract. You can’t see it. It’s not intuitive to people what the electric field is and what it does, so you have to explain that and you can’t do it with equations. It’s not easy for everyone to comprehend the physics and theory behind it.

What do you like about science?

I like the sense of discovery. I like that science involves exploring new territory and doing new things. Within the scientific community, you’re always working with this huge global community of scientists. That’s an aspect I love.

Deepening our understanding of the mechanism

Novocure’s Director of Science Ze’ev Bomzon joined the company in April 2014. He uses his background in physics and cell mechanics to lead a team of researchers at Novocure’s facility in Israel.

Effectively communicating Novocure’s science

Director of Science Ze’ev Bomzon recognizes the necessity of effectively explaining Novocure’s technology – which bridges physics and biology – to researchers of various scientific backgrounds. “We’re always developing new tools to educate people.”