While often associated with good health, the “glow” of a tan is the opposite of healthy; it can injure your skin. Tanning damages your skin cells and can lead to skin cancers. Among skin cancers, melanoma is the deadliest type. It develops in skin cells that produce melanin (the pigment that gives your skin its color). Men are more likely to develop melanoma. Until recently, scientists thought that more men had melanoma because they didn’t wear sunscreen and did not go to the doctor as frequently as women.
Our lab analyzed 1000 melanoma patients, and we identified a gene called DDX3X, which was found to be altered only in male melanoma patients (1). (The alteration of this gene were caused by the UV from the sun.) The fact that only males have a non-functional version of DDX3X could explain why more men are diagnosed with melanoma than women.
DDX3X is a gene located on the X chromosome. Humans have 46 chromosomes where genes are located and encode the blueprints for our bodies to function. Among these 46 chromosomes, we have 2 chromosomes associated with sex. Females have 2 X chromosomes and males have one X and one Y chromosome. Women have 2 copies of DDX3X since they have 2X chromosomes, if one is not functional, they still have one DDX3X to function in its place. However, men have only one copy of DDX3X because they have only one X chromosome. To visualize this, let’s use the idea of the flat tire, women can have a flat tire and they’ll be ok since they have a spare tire (the second functional copy of DDX3X) so they may be less likely to develop melanoma.
However, males do not have spare tire (only a non-functional copy of DDX3X). If they have a flat, there is no backup solution: they may be more likely to develop melanoma.
To verify this hypothesis, I work with skin cancer cells from patient tumors, and I test different drugs targeting DDX3X. I use advanced genetic techniques such as molecular scissors to cut DDX3X from my cells to mimic patient data.
We have collected promising results showing that the alteration of DDX3X could lead to melanoma specifically in males. The goal of my project is to better understand what is happening in these melanomas and to find a way to optimize a personalized care, and this could lead to a novel therapeutic strategy for male melanoma patients. I believe these findings will have broad implications for other cancers where sex differences in incidence and disease progression are observed.
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