Researchers have gained further insight into how the lack of oxygen, or hypoxia, contributes to the progression of melanoma, identifying hypoxia-regulated genes that could direct melanoma diagnosis and treatment.
Their findings revealed 10 genes associated with the amount of time it takes the melanoma to move from the original tumor to the rest of the body. Targeting those genes could potentially improve the prognosis of such patients.
Hypoxia drives numerous gene expression changes that contribute to the progression of many types of cancer. In melanoma, increased expression of HIF1α — hypoxia’s major sensor — is associated with drug resistance, increased metastatic potential and poor prognosis, but the genes associated with such outcomes are not fully known.
Researchers at the National Institutes of Health (NIH) have now identified 40 genes that are regulated by HIF1α in melanoma cells, 10 of which were linked with the time it took for the disease to spread from its original site to other areas of the body.
“These newly identified genes and genetic pathways in primary melanoma could give researchers new targets for developing personalized treatments for melanoma, and potentially other cancers,” the study’s lead author, Stacie Loftus, PhD, said in a press release. “In addition, changes in how the genes are expressed (turned on or off) could be used in the future to predict how and when the cancer cells will spread to other parts of the body and how fast they will grow.”
The findings may also help understand how a hypoxic environment signals to melanoma cells telling them to move to a different site of the body. Identifying which genes are involved in the metastatic process could lead to the identification of biomarkers that predict patients more likely to develop metastasis and in need for more aggressive treatments.
“In many ways, melanoma is a poster child for precision medicine,” said Loftus, a staff scientist in the Genetic Disease Research Branch at the NIH’s National Human Genome Research Institute. “Current therapies in clinical trials are focused on targeting genetic changes in tumors and helping to boost one’s immune system to fight the cancer cells. Identifying how cells respond to their surrounding environment is important information that can be used to help guide treatment decisions for patients.”