Tuesday, 20 November 2012

Irreversible Electroporation

The three main arms of cancer treatments remain surgery, chemotherapy and radiotherapy - these still form the core treatments for most cancers. Arguably the set of treatments called ablative therapies should be added to that list. These include photodynamic therapy, cryoablation, and radio-frequency or microwave ablation. While these treatments work in different ways, they have some common features, they all:

  • physically attack tumours (with heat, cold, laser light etc.)
  • can be re-applied (i.e. resistance to treatments doesn't set in)
  • side-effects are local and easily controlled
  • are little used compared to surgery, chemo and radiotherapy

The last point is an important one, as these treatments have excellent safety profiles and can be targeted to achieve good rates of local control of tumours. The downside is that these treatments have to be applied to individual tumours rather than being able to systemically control widely spread disease. However, when used with other treatments these ablative treatments can make a huge difference to outcomes. As a bonus, for those with mutated tumour suppressor genes like TP53 (i.e. patients with Li Fraumeni Syndrome), there are no unwanted long term risks of other cancers due to DNA damage in surrounding tissues.

The new kid on the block as regards these ablative therapies is irreversible electropration (normally abbreviated as IRE). In this treatment small electrodes (around 1mm long) are implanted on either side of a tumour and then very high currents are pulsed through the tumour for a short period (seconds). The high voltage kills the tumour cells but does nothing to non-tumour cells. In plain terms, the tumours are electrocuted but the rest of the tissues are fine. And, as a bonus, and in common with some of the other ablative therapies the tumour kill is a type that can cause an immune response in which the immune environment changes and the system kicks in to attack the tumour as well - which holds the promise of a systemic effect from a local treatment.

This new treatment is not widely used yet, but it has been used in patients, it's not just another one of these treatments that is still working its way through the pre-clinical phase of working with rats and other animals. Initial results are impressive and a phase II trial is on-going in the United States. So far it has been used with liver and pancreatic cancers primarily, but there is no reason to believe that it will be limited to these cancers only. In fact a recent paper 'Immunologic Response to Tumor Ablationwith Irreversible Electroporation' used IRE on rats with osteosarcoma, opening up the possibility that finally we'll have a new option against this horrific disease.

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