Recently, scientists in Sydney and Melbourne found that follistatin, a natural hormone in human body, not only greatly improves the chemotherapy efficacy of lung cancer patients, but also prevents the serious side effects of kidney damage caused by chemotherapy.
This new idea of ​​cancer treatment for "one stone and two birds" has been successfully verified in a mouse model, and the results were recently published in Science Translational Medicine. The study was the result of a collaboration between the Garvan Medical Institute (Sydney), the Hudson Medical Institute (Melbourne), and Paranta Biosicenses. Paranta Biosicenses develops follistatin for the treatment of cystic fibrosis, kidney disease and cancer.
Despite advances in immunotherapy for lung cancer, most patients are still receiving chemotherapy based on cisplatin. However, cisplatin drugs are less than one-third effective, and are often accompanied by severe side effects including kidney damage.
In order to improve the treatment of patients with lung cancer, Dr. Neil Watkins, Professor of Cancer Biology at the Garvan Institute, and his team, Dr. Kieren Marini of the Hudson Institute, used the whole gene combination to screen for lethal RNA interference and determined the activin signal. It is a key intermediary for innate platinum resistance. Activin A and growth differentiation factor 11 (GDF11) in the transforming growth factor-beta (TGFβ) superfamily ligand utilize their cognate receptors via the TGFβ-activated kinase 1 (TAK1) signaling pathway, rather than through the SMAD transcription factor family Signaling pathways mediate resistance.
Dr. Watkins said: "In chemotherapy-resistant tumors in mice, activin signaling is turned on by chemotherapy-induced damage. Cancer cells can then recruit activins to protect themselves. At the same time, when the activin signal is turned on, It promotes kidney damage."
Fortunately for Dr. Watkins (who was at the Hudson Institute), the key to stopping activin was across the corridor. “Good ideas come from the most unexpected places,†Dr. Watkins said. “We talked to a neighbor who was Dr. David de Kretser, one of the pioneers of reproductive biology in Australia.â€
In the 1980s, at Monash University, Dr. Kretser discovered the naturally occurring hormone follistatin, which blocks activins. He founded Paranta Biosciences in 2011. Dr. Watkins said: "When we talk about the results of lung cancer, he suggested that we try to use follistatin in the mouse model, and you will know the rest."
Dr. Watkins and his team tested follistatin. The experimental results show that in mice, follistatin combined with platinum-based chemotherapy can lead to lung tumor shrinkage and make more mice survive longer. It is worth noting that they found that kidney damage was also prevented. Follistatin overcomes cisplatin resistance by inhibiting activin receptor signaling or by blocking activin A and GDF11. Consistent with the role of activin signaling in acute kidney injury, both therapeutic interventions alleviate acute cisplatin-induced nephrotoxicity, an important side effect of cisplatin dose limitation. This cancer specifically enhances platinum-induced cell death and may significantly improve the safety and efficacy of chemotherapy in patients with lung cancer.
Dr. Watkins believes that the use of follistatin may be a safe and effective method to make cisplatin chemotherapy more effective in lung cancer. “Because follistatin is a hormone already found in humans, it is less likely to be toxic than other drugs used to reduce chemoresistance.†Dr. Watkins now plans to study other common platinum-based chemotherapy tumors, such as the bladder. Cancer and head and neck cancer.
The first author of the article, Dr. Marini, said: "Combination therapy that reduces side effects and enhances chemotherapy is rare in cancer research. Many people have heard of the devastating side effects of chemotherapy on cancer patients. Our findings not only improve the effectiveness of platinum-based chemotherapy, but also provide patients with a better quality of life by preventing kidney damage."
Dr. Watkins and his team's pioneering research with Paranta Biosciences laid the foundation for bringing this combination therapy strategy to clinical research.
For Dr. Kretser, a distinguished scientist at the Hudson Institute who served as Victoria's Governor in 2006-2011, these results provide a good example of the interdisciplinary special strengths. Dr. Kretser said: "I can never predict that as a reproductive endocrinologist, one day I will conduct research in the field of inflammation and tissue repair."
Regarding the occasional situation that led to this discovery, Dr. Watkins wanted to say to his peers: "Open your eyes, open your ears, interact with your colleagues, and develop your imagination. The answers you are looking for may be closer than you think."
Reference materials:
[1] Turbo-charging chemotherapy for lung cancer
[2] Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy
Original title: Frontier | This natural hormone, is expected to improve the efficacy of chemotherapy
Source: WuXi PharmaTech
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