Palladium-activated prodrug therapy: a novel focal therapy for localised cancers of unmet need

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Despite significant advances in the diagnosis and treatment of the earliest stages of cancer, the highest life-threatening risks and therapeutic challenges still remain in developing effective treatment of patients diagnosed with locally advanced or metastatic tumours. For most localised tumours the current treatment is surgical resection, often followed by adjuvant radiotherapy and/or chemotherapy. The potential benefit of such therapies in any stage of the cancer must be weighed against possible adverse effects that can severely impair a patient's quality of life. Unfortunately, even with adjuvant chemotherapy to treat some aggressive cancers like glioblastoma multiforme, the median survival is only improved around 2 months, while associated side effects are very severe. In addition, for localised prostate cancer, significant controversy remains on the optimal treatment options. Due to side effects (incontinence, impotence, bowel problems) of existing treatments (surgery or radiotherapy), current standard of care is active surveillance consisting of regular hospital tests (e.g. prostate biopsies and MRI scans), aimed at deferring intervention. Because of the lack of therapies providing a better balance between treatment efficacy and related toxicities, many of these cancers eventually evolve into a more aggressive form with increased risk of pre-mature death. Therefore, what is needed then are novel drug delivery strategies that can reduce the side effect profile of the treatment whilst maximising therapeutic efficacy. To provide a safer and more effective strategy to those localised cancers, we have devised a novel therapeutic approach that will allow concentrating drug activity only at the cancer area, thereby reducing the severe adverse effects associated with chemotherapy. The technology is based on a novel strategy pioneered at the Edinburgh Cancer Research Centre at the University of Edinburgh that enables full control over where chemotherapy takes action through the use of solid metal devices made of an element called palladium. This metal, which is completely safe to patients (it is already employed in dentistry), can be shaped into implantable devices and possesses exceptional chemical properties that facilitate the local release of anticancer drugs. By implantation inside localised tumour, orally-given drug precursors will only become "active" at the cancer site upon interaction with the palladium device. Given the reusability of this device, this treatment could be repeated as many times as necessary. The unique modulatory capabilities of this novel approach will not only reduce drug presence in healthy organs but will also facilitate personalized treatments to be implemented according to the progression and severity of the disease, thereby reducing side effects and maximizing the efficacy of the therapy. Due to its novelty, such healthcare technology will make a major impact in the Pharma sector and, in turn, in the NHS and people of the UK and worldwide by improving the quality of life and life expectancy of patients suffering from untreatable tumours.