Nav: Home

Turbo-charging chemotherapy for lung cancer

July 25, 2018

A naturally occurring hormone could help make chemotherapy much more effective for many Australians with lung cancer, according to new findings from Sydney and Melbourne researchers.

And the hormone - known as follistatin - also appears to prevent kidney damage, a serious side effect of chemotherapy.

The promising new 'two birds, one stone' treatment approach, which was successful in mice, is published in Science Translational Medicine today. It is the result of a collaborative effort between researchers at the Garvan Institute for Medical Research (Sydney) and the Hudson Institute of Medical Research (Melbourne), along with the biotechnology company Paranta Biosciences Limited, which is developing follistatin as a potential therapy for cystic fibrosis, kidney disease and cancer.

Despite advances in immunotherapy for lung cancer, most patients are still treated with chemotherapy based on a drug called cisplatin. However, less than a 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 (Petre Chair in Cancer Biology, Garvan) and his team, including Dr Kieren Marini (Hudson Institute), 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," says Prof Watkins. "Cancer cells can then enlist activin to protect themselves. At the same time, when activin is switched on, it promotes kidney injury."

Luckily for Prof Watkins (who began the research at Hudson Institute), the key to blocking activin happened to be across the hall.

"Good ideas come from the most unexpected places, " says Prof Watkins. "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."

In the 1980s, while at Monash University, 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, he suggested we try follistatin in mouse models" says Prof Watkins "and the rest is history."

Prof Watkins and his team put follistatin to the test. They found that, in mice, treatment of follistatin in combination with platinum chemotherapy caused lung tumours to shrink and more animals to survive longer. Remarkably, they found that kidney damage was also prevented.

"Discoveries like this one - a combination therapy that actually reduces damage while improving effectiveness of chemotherapy - are exceedingly rare in cancer research," says Dr Marini, who undertook the research as part of his PhD at Hudson Institute.

The pioneering research performed by Prof Watkins and his team in collaboration with Paranta Biosciences has laid the foundation to move this combination strategy to a clinical setting.

"Many of us have heard about the devastating side effects of chemotherapy in cancer patients. 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," says Dr Marini.

For Prof de Kretser, a Hudson Institute Distinguished Scientist and the Governor of Victoria from 2006-2011, these results provide a great example of the remarkable benefits of reaching across disciplines. "I could never have predicted," says Prof de Kretser, "that as a reproductive endocrinologist, someday I would end up working in inflammation and tissue repair."

Prof Watkins says 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."

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

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. The answers you're looking for might be closer than you think."
-end-
This research was supported by the Petre Foundation, the Victorian Cancer Agency, Cancer Council NSW, the St Vincent's Clinic Foundation, Hudson Institute of Medical Research, Paranta Biosciences, NHMRC Australia, and the Victorian Government's Operational Infrastructure Support Program.

Garvan Institute of Medical Research

Related Lung Cancer Articles:

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.
Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.
Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.
Better equipped in the fight against lung cancer
Lung cancer is the third most common type of cancer in Germany and the disease affects both men and women.
New liquid biopsy-based cancer model reveals data on deadly lung cancer
Small cell lung cancer (SCLC) accounts for 14 percent of all lung cancers and is often rapidly resistant to chemotherapy resulting in poor clinical outcomes.
Cancer drug leads to 'drastic decrease' in HIV infection in lung cancer patient
Doctors in France have found the first evidence that a cancer drug may be able to eradicate HIV-infected cells in humans.
Air pollution is associated with cancer mortality beyond lung cancer
A large scale epidemiological study associates some air pollutants with kidney, bladder and colorectal cancer death.
Free lung-cancer screening in the Augusta area finds more than double the cancer rate of previous screenings
The first year of free lung cancer screening in the Augusta, Ga., area found more than double the rate seen in a previous large, national study as well as a Massachusetts-based screening for this No.
Lung cancer may go undetected in kidney cancer patients
Could lung cancer be hiding in kidney cancer patients? Researchers with the Harold C.
More Lung Cancer News and Lung Cancer Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.