"Double punch" treatment fights cancer while reducing kidney damage side effects
Cancer treatment is often a case of robbing Peter to pay Paul. You may well have some success with chemotherapy, but subsequent damage to otherwise healthy organs and tissue is a trade-off that clinicians and patients have had to juggle with for decades. But, thanks to a chance meeting at the Hudson Institute in Melbourne, lung cancer patients could be looking at more effective chemo with fewer side effects.
"Many of us have heard about the devastating side effects of chemotherapy in cancer patients," says researcher Dr Marini from the Hudson Institute. "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."
Lung cancer is commonly treated with platinum chemotherapy based on a drug called cisplatin. However, less than a third of patients will see any benefit, and often develop serious side effects, including kidney damage. In their research, Professor Neil Watkins (Petre Chair in Cancer Biology, Garvan Institute) and his team, including Dr Kieren Marini (Hudson Institute), found the protein activin to be a primary culprit, both in chemotherapy resistance and chemotherapy-induced kidney damage.
"In chemotherapy-resistant tumors in mice, activin gets switched on in response to the damage caused by chemotherapy," said Prof Watkins. "Cancer cells can then enlist activin to protect themselves. At the same time, when activin is switched on, it promotes kidney injury."
This is where the chance meeting comes into play. Across the hall from Prof Watkins' lab at the Hudson Institute (where he began his research) was none other than the founder of Paranta Biosciences, Professor David de Kretser, the scientist who in the 1980s discovered the hormone follistatin – which just so happens to block activin.
"As we discussed our results in lung cancer, he suggested we try follistatin in mouse models, and the rest is history," said Professor Watkins.
Follistatin is a naturally occurring hormone which seems to pack a double punch, not only fighting lung cancer, but preventing the kidney damage common with traditional chemotherapy.
The "double punch" treatment was trialed successfully in mice and subsequently published in the journal Science Translational Medicine. The findings are the result of a collaboration between researchers at the Garvan Institute for Medical Research (Sydney) and the Hudson Institute of Medical Research (Melbourne), along with Paranta Biosciences (which is developing follistatin as a potential therapy for cystic fibrosis, kidney disease and now, cancer). The success of their research means this combination strategy is set to move to a clinical setting soon.
"Discoveries like this one – a combination therapy that actually reduces damage while improving effectiveness of chemotherapy – are exceedingly rare in cancer research," said Dr Marini.
Professor Watkins says that the use of follistatin is likely to be a safe and effective approach to making chemotherapy more effective in lung cancer treatment. "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 explains.
Prof Watkins isn't resting on his laurels just yet and plans to study other cancers such as bladder, head and neck cancer which are commonly treated with platinum chemotherapy. In thinking about the serendipitous circumstances that led to this discovery, Prof Watkins has a message for all scientists.
"Keep your eyes and ears open, engage with your colleagues, and nurture your imagination, he says. "The answers you're looking for might be closer than you think."