Flicking the Switch! Turning Drug-Resistant Melanoma into Drug-Sensitive Melanoma

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1. Please give a summary of your research.

Melanoma (a type of skin cancer) has one of the highest cure rates of any cancer- but only at the early stages! Once it spreads, it can be difficult to treat due to problems with upfront and acquired drug resistance. Recently, researchers have linked two known distinct ‘cell states’ in melanoma as being either ‘drug-sensitive’ or ‘drug-resistant’. Interestingly, colleagues and I have found evidence to suggest that patient’s melanomas can change from a ‘drug-sensitive’ to a ‘drug-resistant’ cell state during the course of therapy (an example of acquired resistance). There have been some isolated reports exploring the mechanisms behind this ‘switch’, but no one has yet performed an extensive unbiased experiment to comprehensively identify the genes responsible for causing this switch. My research is trying to fill this void by systematically turning on, and off, every gene in the human genome to see its effect on melanoma cells. Once I’ve identified the genes that can cause a switch, the concept is pretty simple: develop new treatment strategies to switch ‘drug-resistant’ cells into ‘drug-sensitive’ cells so that we can combine this with our existing therapies to delay resistance, and improve long term survival for late-stage melanoma patients. 

2. Please include any additional details you would like to share

This project is building on from research I started in Boston, including data that contributed to a landmark paper published in Science (Tirosh et al. 2016. 352 (6282): 189-196). Since returning to Australia, I have developed a method crucial for competing this project by identifying unique cell-surface markers for each cell-state (this method is currently being prepared for submission in a journal publication). I now have all the pieces in place to perform the systematic turning of genes on and off (using genome-scale CRISPR-knockout and CRISPR-activation). These experiments are quite technical, and although I have experience in these platforms, I will be working with collaborators at the Hudson Medical Research Institute Centre of Functional Genomics. Lastly, understanding the genes that can switch cell states in melanoma may also have flow-on benefits in understanding a wide range of other cancers and how they become resistant to therapies. This is because the drug-resistant cell state we see in melanoma is reminiscent of other drug-resistant cell-states seen in other cancers, including breast and colorectal cancer. If you would like to hear more about my research or my adventures in science communication, follow me on Twitter @the_funkydr or check out my LinkedIn profile

Comments

4
Laura Bray
4 months ago

Great research Ken, keep up the good work!

Jordan Debono
4 months ago

Good luck!!

Lynn Dutton
4 months ago

Great work Dr Ken!

Darren Regester
4 months ago

Amazing! Fantastic work Ken.

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Dr Ken Dutton-Regester completed his studies at the QIMR Berghofer Medical Research Institute and obtained his doctorate with a focus on melanoma genetics from the Queensland University of Technolo...

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