Australian scientists, inventors and surgeons worked together in ground-breaking research that has lead to the discovery of a way to slow down the growth of deadly asbestos-related cancer malignant pleural mesothelioma.
The break-through underpins a clinical trial due to start in six weeks.
More than 10,000 Australians have died since the early 1980s, with more than 25,000 expected to die over the next four decades, because of mesothelioma, an asbestos-related cancer. The cancer can take up to 40 years to develop.
At a ceremony on Asbestos Memorial Day, Friday November 29, Asbestos Diseases Research Institute senior researcher Glen Reid announced the research, which has just been published in the prestigious Annals of Oncology medical journal, was a flag of hope to patients. “Malignant pleural mesothelioma has proved impossible to treat. Patients normally die within 18 months of diagnosis. This research has shown remarkable results that may be useful in other types of tumours as well.”
Dr Reid and Professor Nico van Zandwijk, who will lead the clinical trial of a new drug resulting from the research, have worked on the project for three years, almost since the founding of the medical research institute where the project is based.
ADRI researchers teamed up with a Sydney-based biotech company, EnGenelC, to use a futuristic new drug delivery system that relies nanotechnology and guiding antibodies. Using animal models, human mesothelioma tumours were treated with antibody-guided minicells containing microRNA mimics – a combination dubbed TargomiRs. “We have found an amazing inhibition of tumour growth. The results were far in excess of what have been seen with other experimental therapies in this model, and we are very excited about it,” said Dr Reid.
The studies were done together with Professor Brian McCaughan from the Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital, who operates on patients with mesothelioma, and provided the tissue samples used in the research.
Mathew Klintfalt, whose mother Carol Klintfalt suffers from mesothelioma, says the discovery is important not just for people of his mother’s generation who were exposed to asbestos before it was banned in 2003, but also people his own age currently being exposed to it
“It’s still out there. We’re a generation of first home-owners. We rip into our new house on DIY renovations, and don’t realise the dangers of asbestos lurking in the roof tiles, cladding the old shed out the back, and in the water and sewage pipes. There are still generations to come who will be affected by this stuff.”
Mathew Klintfalt says the research results give all patients, present and future, hope for a cure.
ADRI media consultant Ellie Martel: 0448 473 877.
Australia has the world’s highest incidence of malignant mesothelioma per capita, with more than 700 new cases diagnosed each year, which is due to the widespread use of the known carcinogen, asbestos. It is estimated that the incidence of malignant mesothelioma will continue to increase for the next 10 to 20 years.
As a response to the increasing incidence of malignant mesothelioma, the Asbestos Diseases Research Institute (ADRI) located in the Bernie Banton Centre, was opened in January 2009 by the then Prime Minister, the Hon Kevin Rudd.
The ADRI/ Bernie Banton Centre was established by the Asbestos Diseases Research Foundation (ADRF), a charitable, not-for-profit foundation dedicated to assist and support the research efforts of ADRI into asbestos-related diseases.
Before his death in 2007, Bernie Banton campaigned vigorously for the rights of those who suffered, like himself, from asbestos-related diseases. This state-of-the-art research facility on the Concord Hospital Campus was named in his honour.
The research (from Annals of Oncology):
Background: Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches to therapy are needed. Reduced expression of miR-15/16 in a range of cancer types has suggested a tumour suppressor function for these microRNAs, and re-expression has been shown to inhibit tumour cell proliferation. The miR-15/16 status in MPM is largely unknown.
Materials and methods: MicroRNA expression was analysed by TaqMan-based RT-qPCR in MPM tumour specimens and cell lines. MicroRNA expression was restored in vitro using microRNA mimics, and effects on proliferation, drug sensitivity and target gene expression were assessed. Xenograft-bearing mice were treated with miR-16 mimic packaged in minicells targeted with epidermal growth factor receptor (EGFR)-specific antibodies.
Results: Expression of the miR-15 family was consistently downregulated in MPM tumour specimens and cell lines. A decrease of 4- to 22-fold was found when tumour specimens were compared with normal pleura. When MPM cell lines were compared with the normal mesothelial cell line MeT-5A, the downregulation of miR-15/16 was 2- to 10-fold. Using synthetic mimics to restore miR-15/16 expression led to growth inhibition in MPM cell lines but not in MeT-5A cells. Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine. In xenograft-bearing nude mice, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of MPM tumour growth.
Conclusions: The miR-15/16 family is downregulated and has tumour suppressor function in MPM. Restoring miR-16 expression represents a novel therapeutic approach for MPM.