Melanoma, a relatively rare but deadly skin cancer, has been shown to switch differentiation states -- that is, to regress to an earlier stage of development -- which can lead it to become resistant to treatment. Now, UCLA researchers led by Dr. Thomas Graeber have found that melanomas can be divided into four distinct subtypes according to their stages of differentiation. Cell subtypes that de-differentiated -- meaning they reverted back to a less-mature cell -- showed sensitivity to a type of self-inflicted cell death called ferroptosis.

The research also showed that certain subtypes of melanoma cells could be successfully treated using multiple therapies in combination with ferroptosis-inducing drugs. 

The study, published online in Cancer Cell, is the first to link ferroptosis to melanoma differentiation states. The melanoma subtypes characterize the four steps along a trajectory taken by melanoma cells as they respond to exongenous stresses, such as drug treatments. Drugs that target de-differentiated melanomas could complement existing therapies, which are effective against differentiated melanoma cells.

"Furthermore, these standard-of-care therapies can induce de-differentiation, and thus in a co-treatment setting, ferroptosis induction can potentially block melanoma cells attempting to take this escape route," Graeber said.

Dr. Graeber received a voucher from CTSI to conduct gene-expression profiling.

In collaboration with Dr. Graeber, UCLA Technology Development Group has filed a provisional application based on this work. For more information, please contact UCLA TDG at innovation@tdg.ucla.edu

Further Reading:

The full UCLA press release
The Cancer Cell publication. "Multistage Cell Differentiation Defines Melanoma Subtypes with Differential Vulnerability to Drug-Induced Iron-Dependent Oxidative Stress."
Medical News Today article

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