Image Credit: Rhoda Baer
A multidisciplinary team of medics and engineers at the University of Oxford have designed and tested a novel and potentially highly significant cancer targeting process, which uses ultrasound to direct chemotherapeutic agents to tumours. The findings of this study have been published in the Lancet, with the potential to increase the efficacy of chemotherapy.
In chemotherapy, chemotherapeutic agents are introduced to the body via the bloodstream; they circulate around the entire body and will hopefully reach the cancerous lesion. In order to bring benefits to the patient, these chemicals must reach a therapeutic concentration in the tissues affected by the tumour, which brings with it a problem. Chemotherapeutic agents are poisons, which have toxic effects such as inhibiting mitosis (cell division), in order to prevent cancerous cells spreading. However, healthy cells are inevitably killed as well, causing many of the side-effects so familiar to us, such as hair and weight loss. If medics can target the chemotherapeutic agents directly to the cancerous tissues, not only can they increase the likelihood that the tumour is actually affected, but the overall dose can be reduced, potentially lessening side-effects.
In this new procedure, the chemotherapeutic agents are packaged into low-temperature sensitive liposomes (small sacs of phospholipids) that are injected into the blood. Above 39.5℃, the structure of the liposomes break down, releasing their contents. Using highly focussed ultrasound, the cancerous tissues can be heated above this temperature, therefore targeting the chemicals to the tumours.
The phase 1 clinical trial tested the effect of doxorubicin on 10 individuals suffering from inoperable liver cancers and the authors believe that they have achieved a proof of concept for this procedure:
“Overall, this prospective study shows for the first time in a clinical setting the safety, feasibility, and potential for therapeutic benefit of ultrasound-triggered release of LTLD in otherwise chemorefractory tumours”
The results for all 10 subjects show that there were increased level of drugs localised in the cancerous tissue when compared to pre-ultrasound conditions, with concentrations being 3.7 times greater on average.
Moreover, Professor Mark Middleton (the Principal Investigator of the study) indicates that this procedure could have applications far beyond increasing doxorubicin concentrations in treatment of liver cancers:
“The ability of ultrasound to increase the dose and distribution of drug within those regions raises the possibility of eliciting a response in several difficult-to-treat solid tumours. This opens the way not only to making more of current drugs but also targeting new agents where they need to be most effective. We can now begin to realize the promise of precision cancer medicine.”
Many teams around the world are researching the application of this procedure to the treatment of different types of cancer, using different types of drugs.