Reversing chemo-resistance in lung cancer

Prof Neil Watkins

Professor David (Neil) Watkins

Garvan Institute of Medical ResearchFunding duration: 2015–2017

Professor David Watkins and his team have discovered a previously unknown reason for treatment resistance in lung cancer. The team have also discovered a naturally occurring hormone that could be used to reverse this treatment resistance and improve the effectiveness of chemotherapy.

Background

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, despite best efforts, less than 20% of patients will respond to this treatment because lung adenocarcinoma is very resistant to cis-platinum.

In this project, Professor Watkins and his team have used the results of a whole-genome screen to identify new therapeutic targets that can dramatically increase the effectiveness of cis-platinum in lung cancer.

The research

By conducting a whole-genome screen of lung cancer cells, the research team has discovered a previously unknown reason 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. Follistatin is a naturally occurring hormone in the body that can block the function of activin. Professor Watkins has now shown that follistatin can reverse resistance to cis-platinum chemotherapy in the lab.

The impact

Based on their findings, the team has formed a partnership with the researchers who discovered follistatin and a biotechnology company that is already developing the hormone as an anti-inflammatory drug. Through this new collaboration, Professor Watkins and his team have the opportunity to develop follistatin for clinical trials in lung cancer. Improving the effectiveness of cis-platinum chemotherapy has the potential to significantly improve outcomes for the many patients with lung cancer.

Lead ResearcherResearch Team

Professor David (Neil) Watkins
Garvan Institute of Medical Research

Hudson Institute of Medical Research
Paranta Biosciences


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