Make resistant melanoma drug-sensitive again!

Sparrho Hero, Ken Dutton-Regester explains in fun science communication video

Aussie researcher, Dr Ken Dutton-Regester recently co-wrote a 3 Minute Sparrho Digest about how a hairloss-causing gene can be a force for good in fighting melanoma and other cancers.

He also submitted a science communication video for the Centenary Institute Medical Innovation Award 2018 explaining how the deadliest type of skin cancer, melanoma can be switched from drug-resistant to drug-sensitive. Making later-stage melanoma treatable again would be great news for patients, but how could it be done?

Trying to understand why treatment makes melanoma drug resistant

As Ken explains, melanoma 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 patients’ 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— he explains.

Hunting for the ‘switch’

Ken and his team has set out to identify the mechanism responsible for drug resistance by systematically turning on, and off, every gene in the human genome (using genome-scale CRISPR-knockout and CRISPR-activation) 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”

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 — says Ken.

Find out more about Ken’s research on his Sparrho Profile and on Twitter.