More effective chemo for lung cancer patients

A naturally occurring hormone called follistatin could help make chemotherapy much more effective for lung cancer patients, while also preventing kidney damage — a serious side effect of the treatment.

That’s according to a collaborative study between Sydney’s Garvan Institute for Medical Research, Melbourne’s Hudson Institute of Medical Research and biotechnology company Paranta Biosciences, which is developing follistatin as a potential therapy for cystic fibrosis, kidney disease and cancer. The results of the study have been published in the journal Science Translational Medicine.

Despite advances in immunotherapy for lung cancer, most patients are still treated with chemotherapy based on a drug called cisplatin. However, less than one-third of these patients will see benefits, and they often develop serious side effects including kidney damage.

In an effort to improve outcomes for lung cancer patients, Professor Neil Watkins and his team discovered that a protein called activin is a culprit in both chemotherapy resistance and chemotherapy-induced kidney damage.

“In chemotherapy-resistant tumours in mice, activin gets switched on in response to the damage caused by chemotherapy,” said Professor Watkins, currently based at Garvan. “Cancer cells can then enlist activin to protect themselves. At the same time, when activin is switched on, it promotes kidney injury.”

Luckily for Professor Watkins — who began the research at the Hudson Institute — the key to blocking activin happened to be across the hall. “We spoke to one of our neighbours,” he said, “and that neighbour was none other than Professor David de Kretser — one of the pioneers of reproductive biology in Australia.”

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

“As we discussed our results in lung cancer,” Professor Watkins said, “he suggested we try follistatin in mouse models — and the rest is history.”

The team found that, in mice, treatment of follistatin in combination with platinum chemotherapy caused lung tumours to shrink and more animals to survive longer. They also found that kidney damage was prevented.

“Discoveries like this one — a combination therapy that actually reduces damage while improving effectiveness of chemotherapy — are exceedingly rare in cancer research,” said Hudson’s Dr Kieren Marini, who undertook the research as part of his PhD.

“Our discovery has the potential to not only increase the effectiveness of platinum chemotherapy, but also give patients a better quality of life by preventing kidney damage.”

According to Professor Watkins, the use of follistatin is likely to be a safe and effective approach to making chemotherapy more effective in lung cancer. “Because follistatin is a hormone already found in the human body, there is much less potential for toxicity than with other drugs used to reduce chemoresistance,” he said.

For Professor de Kretser, the results provide a great example of the remarkable benefits of reaching across disciplines. “I could never have predicted that, as a reproductive endocrinologist, someday I would end up working in inflammation and tissue repair,” he said.

Professor Watkins now plans to study other tumours where platinum chemotherapy is commonly used, such as bladder and head and neck cancers. In the meantime, the research has laid the foundation to move the combination strategy to a clinical setting.

Image caption: Professor Neil Watkins with Racheal Zekanovic, Dr Alvaro Rajal and Venessa Chin.