Turbo-charging chemotherapy for lung cancer

26 July 2018 | Professor Karen Canfell

With funding from Cancer Council NSW, researchers have discovered an underlying cause for treatment resistance in lung cancer. The team, led by Professor Neil Watkins at the Garvan Institute of Medical Research, has also discovered a naturally occurring hormone which could be used to reverse this treatment resistance and improve the effectiveness of chemotherapy.

We caught up with Professor Watkins to find out more about the team’s discovery.

Lung cancer is the leading cause of cancer death in NSW. Lung adenocarcinoma is the most common form of the disease, and most patients with this cancer will be treated with combination chemotherapy that includes the agent cis-platinum. However, less than a third of these patients will see benefits, and they often develop serious side effects including kidney damage.

A naturally occurring hormone could help make chemotherapy much more effective for many Australians with lung cancer, according to the new findings.

Unlocking the secret to chemo-resistance

By conducting a whole genome screen of lung cancer cells, the research team discovered an underlying cause for cis-platinum resistance. Lung cancer cells can resist the treatment using a hormone-like molecule called activin. The purpose of activin is to regulate the lung’s response to injury – essentially acting as a survival signal. The team’s data suggests that this mechanism is very common in lung adenocarcinoma.

By blocking activin, the survival signal in the lung would be silenced.

The pathway to breakthrough

Luckily for Prof Watkins the key to blocking activin happened to be across the hall.

“Good ideas come from the most unexpected places. We spoke to one of our neighbours, and that neighbour was none other than Professor David de Kretser, one of the pioneers of reproductive biology in Australia. As we discussed our results in lung cancer, he suggested we try a hormone called follistatin” said Professor Watkins.

Professor David de Kretser discovered follistatin – a naturally occurring hormone which blocks activin – in the 1980s. He founded Paranta Biosciences in 2011 to develop follistatin for clinical use, specifically in the treatment of inflammatory and fibrotic diseases.

Professor Watkins and his team put follistatin to the test. In preclinical experiments, they found treatment of follistatin in combination with platinum chemotherapy caused lung tumours to shrink. Remarkably, they also found this combination therapy prevented kidney damage.

Progressing the research further

The pioneering research performed by Professor Watkins and his team has laid the foundation to move this combination strategy to a clinical setting.

If successful in clinical trials, this new combination therapy could dramatically improve the effectiveness of chemotherapy for lung cancer patients. The discovery also has the potential to give patients a better quality of life by preventing one of the most devastating side effects of chemotherapy in cancer patients.

The team now plans to study other tumours where platinum chemotherapy is commonly used, such as bladder and head and neck cancers.

This research was supported by Cancer Council NSW, Victorian Cancer Agency, the St Vincent’s Clinic Foundation, Hudson Institute of Medical Research, Paranta Biosciences, NHMRC Australia, the Petre Foundation and the Victorian Government’s Operational Infrastructure Support Program.