Does the electric field "detonate" cancer cells? What is the principle behind this black technology?
On the last day of February this year, I happened to see a non-invasive electric field anti-cancer device called Optune approved in Hong Kong.
Non-invasive electric field anti-cancer? The singular cake is really the first time I heard about it.
Strong curiosity drove me to study the principle of Optune electric field anti-cancer.
At that moment, when a specific frequency of therapeutic electric field was applied around the cancer cells that were dividing, I immediately recalled the soundtrack Sabotage in Star Trek 3: Beyond the Stars.
Especially the one that started at 1 minute 52 seconds, " Why~~~ ".
But what I wanted to call out was " Wa~~~ "; at this moment, "Why~~~" shouted, and should be left to cancer cells anyway.
â–² After applying the electric field, the cancer cells burst and the scene is as exciting as Star Trek 3: Beyond the Stars!
So, what is the principle behind the cool anti-cancer black technology that the electric field "detonates" cancer cells?
And while listening to see the singular cake for your analysis.
Turning waste into treasure
Things have to start from 2000.
At the time, Dr. Yoram Palti, who taught at the Technion of Israel, a world-renowned science and engineering university, wanted to bring new treatments to cancer based on his expertise.
â–² Dr. Yoram Palti (novocure.com)
However, Dr. Palti is a biophysical and electrophysiological expert, which at the time was not related to anti-cancer. Fortunately, his understanding of electricity and life is higher than ordinary people.
In fact, cells are composed of basic charged particles, many of the macromolecules that play a role in life activities are charged, and the electrical activity of cells plays an important role in many physiological processes [1], then, In theory, cancer cells are definitely affected by electric fields.
As for which electric field intervention will lead to cancer cell death without harming normal cells, Dr. Palti needs to do research.
â–² Live cancer cell division live broadcast (first round, then split into two)
After consulting a large amount of literature, Dr. Palti found that alternating electric fields can have a wide-ranging impact on living tissue.
Electric fields with frequencies below 1 kHz are low-frequency electric fields that can only interfere with particle motion on the surface of the cell membrane [2]. Its use scene, we are all familiar with, can be used to stimulate nerves, muscles and heart [3,4], and even stimulate bone growth and accelerate fracture healing [5].
And those high frequency electric fields with frequencies above 10 MHz, the physiological effects have completely changed. Its stimulating effect has almost disappeared, replaced by the thermal effect [6]. There are also some applications in this band, such as radiofrequency ablation, an invasive tumor therapy [7].
The most embarrassing is the intermediate frequency electric field with a frequency between 10 kHz and 1 MHz. They neither activate nerves and muscles, nor generate enough heat at low intensity. So for a long time, scientists felt that the IF electric field was very wasteful and had no meaningful biological effects on cells [6].
However, Dr. Palti did not let the IF electric field that nobody loved.
He carefully studied the past studies of the intermediate frequency electric field and found that the intermediate frequency electric field can affect the arrangement of particles inside the cell, and the cells will rotate in the electric field [8-10].
These phenomena have attracted their attention.
So Dr. Palti started his own research in his own garage.
â–² Location of the IF electric field studied by Dr. Palti (onclive.com)
In May 2004, Dr. Palti's research was successfully published in the famous journal Cancer Research [11]. For the first time, an extremely low-intensity (<2V/cm) intermediate frequency electric field (100-300kHZ) can disrupt the mitosis of cancer cells and inhibit the proliferation of cancer cells. It also shows a good tumor growth inhibition effect in mouse models.
They refer to this therapy as Tumor Treating Fields (TTFields). This therapy is not only non-invasive, but does not have any significant side effects.
Electric field "detonates" cancer cells
Written here, Benqi will no longer sell off the cake.
Dr. Palti now knows that the IF electric field "detonates" cancer cells in two ways.
First, in the middle stage of cancer cell division, the electric field affects the formation of spindle microtubules, leading to abnormal chromosome separation, which prevents cancer cells from dividing until apoptosis. Second, at the end of cancer cell division, the electric field pushes the charge toward division. The neck of the cell destroys the structure of the cancer cell and eventually leads to cell death [12].
Let us first look at the first one.
First of all, please take a look at the cells with me.
â–² The middle "X" is the chromosome, the ellipse is the mitochondria, and the two radial ones are the spindles of the dragged chromosome.
The "X"-like substance in the middle of the cell is the chromosome. Our genetic information exists. When the cell is split, the chromosome will be copied first, and then the chromosome will be evenly divided into two under the traction of the spindle. , moving from the middle of the cell to the poles. Then, the cells are sunken from the middle and one cell becomes two.
If the spindle of the traction chromosome is destroyed, the chromosomes cannot be evenly distributed to the two cells, causing the two daughter cells that have been split by the cancer to appear "internal disorder" and eventually collapse.
â–² Look at the cancer cell in the upper right corner, it is splitting
Ok, after knowing this, let's take a look at the effect of the electric field on the formation of the spindle.
The spindle is composed of tubulin.
â–² Cheerful tubulin
Since tubulin is polar, under normal conditions, each tubulin can be automatically assembled into a spindle according to its structure and polarity.
â–² Tubulin is being assembled into a spindle
When we applied the TTFields developed by Dr. Palti to the dividing cells, the tubulin immediately adjusted its direction and remained flush with the electric field lines.
â–² After applying an electric field, tubulin quickly adjusts the angle to keep the polarity and electric field flush
Since TTFields is an alternating electric field with a frequency of 100-300kHZ. This means that the electric field direction of TTFields has to be changed hundreds of thousands of times in one second. This speed makes the tubulin completely dumbfounded, staying in place and the spindle can not be formed.
â–² The alternating electric field of TTFields makes tubulin stay
â–² TTFields cause tubulin to stop assembling into a spindle
In this case, the distribution of chromosomes carrying genetic information is certainly a mess, and eventually the two daughter cells can only go to extinction.
â–² Spindle dissipates, cancer cell "Boom", dead
Let's take a look at the second method of death of cancer cells.
This second method of death is the formation of a "cleavage ditch" between two cancer cells when the cancer cells are recessed inward at the end of the split. This special cell structure causes the alternating electric field lines to accumulate in the depressions to form a non-uniform alternating electric field.
â–² Cell division and depression, causing the electric field lines to bend and converge
This non-uniform alternating electric field causes the charged organelles in the cells to rush into the depression and increase the pressure in the cleavage furrow. Cell division is forced to break, and cancer cells that fail to complete division will also blister, rupture, and eventually die.
â–² The collection of electric field lines causes the separated organelles and chromosomes to re-aggregate in the depression, and the cancer cell division is blocked.
â–² The split can't be completed, the cancer cells are bubbling, rupturing, and dying~
The above is the death of cancer cells under the action of the TTFields alternating electric field.
Some readers may ask, does this not harm healthy cells?
In fact, the reason why cancer is so powerful is mainly the ability of cancer cells to proliferate and invade. Cancer cells proliferate much faster than normal adult somatic cells. Many types of somatic cells in adults even lose the ability to divide and proliferate, such as nerve cells.
In addition, the frequency of TTFields affecting normal is also quite different from that of cancer cells.
â–² Different cell types correspond to alternating electric fields of different frequencies
It is this difference that makes TTFields hardly harm normal somatic cells. This is also the reason for its small side effects.
In addition, although the singularity cake dismantles the above mechanism is very simple, in fact, the process of treatment equipment and treatment are not so simple.
▲ The electric field “detonated†cancer cells live broadcast (this picture is a sequel to the live broadcast of the previous scene, the two cancer cells split under the action of TTFields, and soon died on their own)
Optune is a non-invasive portable device that provides an alternating electric field. Only this hardware is not enough. For accurate treatment and better treatment, Optune also has a matching NovoTAL system.
NovoTAL is a software program that optimizes the layout of a patient's transducer array based on head size and tumor location. The combination of the two guarantees the efficacy of TTFields.
Unparalleled fourth new anti-cancer technology
As for the therapeutic effect of TTFields, it can be seen from the article published in the top medical journal JAMA in 2017. The median progression-free survival increased from 4 months to 6.7 months; the median overall survival increased from 16 months to 20.9 months, and the five-year survival rate increased from 5% to 13% [13].
Other studies have shown that the longer Optune wears, the better the effect: patients who use more than 22 hours a day have a median survival of 25 months and a five-year survival of nearly 30% [14].
â–² Schematic diagram of the treatment process
In fact, due to the excellent efficacy of TTFields, it was approved by the FDA for the treatment of recurrent malignant gliomas in 2011 as the most stringent medical device pre-market approval (PMA). Debut at the same time as immunotherapy.
In 2013, the NCCN guidelines included electric field treatment for the first time. In 2015, TTFields was approved by the FDA for the treatment of newly diagnosed malignant glioblastoma over the age of 22. By 2018, the latest NCCN guidelines will even promote electric field therapy as a category 1 recommendation for the treatment of malignant glioblastoma.
Even in China's "Glioma Diagnosis and Treatment Regulations (2018 Edition)" [15], it is also clearly recommended: "Current research shows that electric field treatment is safe and effective, recommended for new hair GBM (level 1 evidence) and recurrence high level Treatment of glioma (level 2 evidence)."
â–² The development of TTFields (nature.com)
In fact, it can be seen from the research papers in 2004 and 2007 that TTFields can affect the proliferation of a variety of cancer cells. Therefore, its potential use value in other cancers is also very large.
Currently, TTFields is conducting clinical studies in a variety of extracerebral solid tumors including pleural mesothelioma, ovarian cancer, non-small cell lung cancer and pancreatic cancer [16]. Clinical studies of pancreatic cancer and non-small cell lung cancer have entered phase III.
In the foreseeable future, TTFields is expected to expand into more cancers in the same way as immunotherapy.
Source: Singularity Network
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