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Star Wars Day, Bubbles and Why we haven’t cured cancer yet?

3P at the IET "why we haven't cureed cancer yet" Kelvin Lecture on May 4th
 

 

Dr Jack KreindlerProfessor Eleanor Stride

The first Kelvin lecture was held in 1908 by Sylvanus Thomson on the life of Lord Kelvin. This was held in the same Lecture theatre in the IET Savoy Place as the Future Science Eng Talks – the new name for the Kelvin lectures. This year’s event was held on May the fourth, otherwise known as Star Wars day (May the Force for those who haven’t seen Star Wars).

3P were delighted to be invited to exhibit at this prestigious event. One of our Directors, Dr Dave Seaward was in attendance. He had a fascinating evening listening to the lectures and then talking with many of the attendees, near our table top display, at the drinks reception that followed.

The event was thought provoking and explained why we need engineering solutions to current healthcare problems.

Dr Jack Kreindler gave an introductory lecture. Founder of The Centre for Health and Human Performance, this is a physician who wants to bring the Engineering discipline and Artificial Intelligence into medical practice. He works with bioengineers and mathematicians to help medics make better and earlier decisions.
He explained the health care crisis that we find ourselves in. Demand is outstripping supply, and 73% of all western healthcare costs are now taken up with 5 disease groups: Heart failure, Neuro Degenerative diseases such as Parkinson’s, Diabetes (and associated complications), chronic lung diseases (asthma and COPD) and lastly Cancer – more of which later.

Within his lifetime he has seen an extra 20 years of life expectancy. This is seen as a good thing, however as we live longer, the percentage of our life that is disease free is diminishing. On average 20% of our lives are no longer at full health… he is asking the question how can we thrive until 100 years of age?

 Life Expectancy is increasing

He has a dream that we can live to 100 and that the vast majority of those years will be heathy and productive. There is an urgent need to find lower cost ways to predict medical problems before they happen… currently we accumulate so many problems in our bodies before we treat them.

Wearable technology may hold the key. Cutting edge wearables use sensing, telemetry and big data processing techniques. These techniques were originally developed by engineers for Formula 1 motorsport, and now they are commonly used in modern aircraft to predict when maintenance is required and predict problems ahead of time: by way of example a trans-Atlantic aircraft jet engine will generate a half terabyte of data on a return journey. We are at a threshold in medical diagnostics, where wearables will predict COPD or chronic heart failure for just $1 per day.

Jack postulated that engineering is required to close the gap between health span and life span. He went on to show how the use of AI and big data analytics techniques, originally developed to assist elite sports was now able to predict with some accuracy when someone would die, decades in advance!
We can now predict when someone will die decades ahead based on diagnostics and AI
He finished his presentation by telling the story of a gene sequencing pioneer and entrepreneur, Stefan, who has recently been diagnosed with a brain tumor with approximately 12 months to live. Stefan saw the tumor as an engineering challenge so rather than surrounding himself with oncologists he decided to surround himself with biomedical engineers, computer scientists, mathematicians and physicists.

Following on from Jack, the main presentation was made by Oxford University’s Professor Eleanor Stride on “why we haven’t cured cancer yet” and her work on using bubbles to effectively deliver cancer treatments. Could we design, manufacture and deliver ‘stimuli-responsive’ particles directly to the target site? Professor Eleanor Stride, a mechanical engineer by training, believes we can. She introduced her work with ‘microbubbles’, the challenges of new drug delivery strategies and their potential for improving treatment of cancer.

Medical science come a long way. It wasn’t too many years ago that 66% of US deaths were caused by flu: 1900 to be precise when the worldwide life expectancy was 31 (40 in the UK and US). As we have eliminated many diseases our chance of dying from cancer has trebled.
Causing of death in 1900 and now

We have come a long way since Hippocrates came up with the word “cancer” 2500 years ago. At that time the treatment consisted of a good healthy diet, leeches and laxatives! It is only in the last 100 years that real advances in cancer treatment have been made. Despite these extraordinary advances in cancer treatment over the past century, patient survival rates are still quoted in terms of 3 to 5 years, and the impact of new treatments is so varied.

Cancer is caused when normal cell division is disrupted. Our cells have programmed cell death or apoptosis. When this goes wrong cells grow uncontrollably into a cancer. Unregulated cell division creates a mass of cells which become a tumor. As the cells are our cells the immune system cannot identify and deal with tumor cells. These cancer cells don’t die and they choke the surrounding tissue. The cancer needs a blood supply and due to the speed of growth it creates a chaotic open mesh of blood vessels around the outside of the tumor. The inside of the tumor typically has very little blood supply. This is why infusions into the bloodstream of anti-cancerous pharmaceuticals struggle to get to their intended target.

Another challenge with treating cancers is they shut down the lymphatic system designed to drain away excess fluid. Lymphatic cells are crushed by the rapidly growing tumor. Hence fluid isn’t drained away from the tumor and pressure inside increases. This pressure gradient makes it even harder to get anything into a tumor to treat it. This also means that oxygen finds it difficult to diffuse into the tumor. Cells within a tumor become hypoxic (low oxygen) and are known as Zombie cells which don’t respond well to radiotherapy, chemotherapy or immunotherapy. These Zombie cells are very difficult to destroy and this is why treating cancer is so challenging, and also why there is often recurrence. These cells can get into the bloodstream and cause secondary tumors elsewhere in the body.

Despite the above challenges the prognosis for a cancer patient is becoming increasingly positive especially if tumors are diagnosed and treated early. Surgery and radiation treatment were the mainstay of cancer treatment in the first half of the 20th century. Now we can also treat cancer cells with laser microwave ablation, radiofrequency ablation and high intensity ultrasound. These techniques are very effective at destroying primary cancer sites, but they are less effective if the cancer has spread into the blood stream and second tumors have formed.

Hence the use of chemotherapy, which was the other major improvement in cancer treatment: drugs are injected into the bloodstream to “mop-up” and kill cancer cells. Unfortunately a tiny proportion (less than 1%) of a poisonous chemo drug makes it to cancer sites. The rest is absorbed by healthy tissue leading to well documented horrendous side effects.

Immunotherapy is an exciting new treatment that is likely to change the face of cancer treatment over the coming 10-20 years. Immunotherapy switches the immune system back on to identify and destroy cancer cells. Not only does it have a reduced side effect profile, it is also more effective at mopping up cancer cells. Whilst the drugs are effective they still struggle to get deep within the cancer due to the pressure gradient.

Another recent exciting advance is photodynamic therapy which utilizes drugs which only become activated when they are exposed to light. A laser activates the drug at a local site. It is proving effective with breast cancer, prostate cancer and skin cancer. Clearly deep cancers where a laser cannot penetrate cannot be treated this way and patients also have to remain in a low light environment for a period of time to avoid healthy tissue damage. This technique has recently been modified for use with focused high intensity ultrasound to trigger the drug.

Nanoparticles are being investigated (around 250nm diameter) because cancers have a more open structure (300nm) than healthy tissue (100nm). A suitably sized particle can avoid healthy tissue but selectively enter cancers. These larger particles still have to deal with the adverse pressure gradient.

To overcome the pressure gradient, attempts have been made to use small magnetic particles about the size of a red blood cell. These can swim in the presence of an alternating magnetic field and are known as microswimmers. The field has to be applied externally and falls off rapidly. Hemce, they can only currently be applied to surface tumors. This concept has recently been taken a step further with the world’s smallest machines which use chemistry. “Molecular machines” won Sauvage, Stoddart and Feringa a Nobel Price in Chemistry (2016). Although in its infancy this technology could create drugs that could actively swim into tumors.

Recent trials for brain tumors have used ultrasound to generate a pressure wave to enable chemotherapy drugs to enter the tumor more effectively with very promising results. The next step is to use a miniature gas bubble 8 microns across which responds well to ultrasound. It oscillates under ultrasonic excitation, and can thereby enter a tumor against the pressure gradient to deliver chemo drugs. This technique is already working in the lab at Oxford in model tumors.

This still doesn’t overcome the challenge of Zombie cells that do not react with treatments due to low oxygen levels. These bubbles can be filled with oxygen and when combined with ultrasound have been shown to arrest aggressive cancers.
Stopping cancer with microbubbles, ultrasound and oxygen

Professor Stride provided a fascinating insight into what cancers are and why they are so difficult to treat. She also presented some exciting new treatments including microbubbles which she is working on. Both Eleanor and Jack explained why a multidisciplined approach using engineers was going to be essential to solve some of the world’s great healthcare challenges of the 21st century.

If the above summary of their lectures has whetted your appetite for more, the whole lectures are still available to view on the IET website – here.

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