Analysis: While great strides have been made in the last couple of decades, with localised thermal therapy currently being used to treat multiple cancers, it was the inspired work of early intellectuals that planted the seed of this treatment for modern times.

By Gary Hannon, TCD

Cancer has been famously described as a 'more perfect version of ourselves'. This disease shares vast similarity to us, which makes drug design incredibly tricky, while also continually mutating to something more adept to survival then we are.

Cancers can recur when a small portion of their cells with inherent resistance to treatment proliferate weeks, months, or years after exposure and are often incurable at this stage. These resistant cells will not be picked up in a scan or blood test following treatment but lay dormant until another opportunity for growth presents itself.

Ovarian cancer, glioblastoma (brain) cancer, bone cancer and pancreatic cancer are just some notable examples of diseases with a high propensity for recurrence following treatment. It is essential that alternative treatment options are developed to overcome our resilient masters of survival.

Curiously, we may not require a massive leap in innovation for additional treatments, but a closer look into our medical past may provide just enough inspiration. I am speaking specifically of a moment of serendipity presented to Edwin Smith, a Connecticut-born antique collector, who acquired an intriguing scroll from an antique seller in Luxor, Egypt in 1862.

What he didn’t know at the time was that this 15-meter-long papyrus in terrible condition provided some of the earliest documented evidence of medical practice. Dating back to the 17th century BC - and thought to be a copy of an even earlier text originating from 2,500 BC - the now well-known ‘Edwin Smith’s Surgical Papyrus’ was translated to describe 48 medical cases.

Of these, case 39 detailed the use of a ‘fire drill’ - a stick that was rotated rapidly to generate heat - which was pressed against breast tumour tissue as an invasive means of ablating the abnormal growth.

While this may seem a barbaric means of treating a tumour - especially considering anaesthesia didn’t emerge until the mid-to-late 19th century - similar reports of this thermal treatment could be found in Greek and Roman literature from about 500 BC. Was there something about heat that couldn’t be ignored?

One of the 48 cases in 'Edwin Smith's Surgical Papyrus’ shows the use of a 'fire drill' - a stick that was rotated rapidly to generate heat.

Sometimes in science alternative paths indirectly arrive at the same conclusion, reinforcing confidence in a particular school of thought. In 1891, a New York surgeon named William B. Coley began the absurd prospect of injecting individuals bearing inoperable bone cancers with bacteria.

Coley speculated that the resulting bacteria-driven immune activation may also stimulate an immune response against tumours - an idea previously described by the German surgeon Wilhelm Busch, who in 1866 had observed a bone cancer patient go into regression following contraction of erysipelas, a relatively common skin infection.

Remarkably, many of Coley’s patient tumours disappeared following this infection, and the hugely promising field of cancer immunotherapy was established. Important to consider, however, was the inherent fever that was essential for this response. Thermal therapy for cancer had subtly re-entered our thoughts once again.

Over the next hundred years, a hyperthermia revolution took place. The biological mechanisms behind this treatment were established and many techniques to generate heat in tumours underwent extensive clinical investigation. The sensitivity of cancer to heat was found to be due to tumours inherently immature vasculature and their inability to thermoregulate.

Additionally, heat could enhance the effects of chemotherapy and radiation, overcoming conventional treatment resistance. Interest in whole body hyperthermia gave way to more controllable, reproducible, and safer techniques that focused heat directly on the tumour, sparing healthy tissue damage.

These techniques utilised high frequency currents in the form of radiofrequency waves, focused ultrasound and microwaves that generate high temperatures localised to tumours (more than 50°C), not achievable with whole body approaches due to off-target safety concerns.

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From RTÉ Radio One's Today with Claire Byrne, Professor Adrian Bracken of TCD School of Genetics and Microbiology spoke to Claire about some new research in the field of childhood cancer that could lead to a breakthrough.

Moreover, the explosion of interest in nanotechnology has provided another edge to this space. Iron oxide nanoparticles are tiny magnetic materials - one million times smaller than a millimetre - that generate heat when exposed to magnetic fields.

Trillions of these can be injected into the tumour of a patient and the individual exposed to multiple cycles of external magnetic fields, administering continuous localised heat to the tumour safely. This magnetic hyperthermia treatment is now approved for use in glioblastoma, where it can potentiate radiation and prolong survival in these patients against radiation alone.

My own research also tests this treatment in pancreatic cancer, where our project has shown that magnetic hyperthermia can augment the effects of chemotherapy in this disease. This work is now undergoing clinical evaluation in pancreatic cancer patients.

While great strides have been made in the last couple of decades, and localised thermal therapy currently being used to treat multiple cancers, it is important to reflect on the history of this treatment. It was the inspired work of early intellectuals that planted the seed of this treatment for modern times.

While the burning of tumours across ancient Egyptian, Greek and Roman times may seem crude, its influence is still apparent in medical practice today - let’s not let the lessons from our past die out.

Gary Hannon is a postdoctoral researcher at the Nanomedicine and Molecular Imaging Group and Trinity College Dublin. His current research explores the potential of magnetic hyperthermia to treat pancreatic cancer.

The views expressed here are those of the author and do not represent or reflect the views of RTÉ