Gene Inhibiting Assists Chronic Disease Prevention, Targeted Therapy 

According to researchers from Massachusetts General Hospital, an olfactory receptor gene that aids in the sense of smell could play a role in the metastasis of breast cancer to the brain. By inhibiting the gene, OR5B21, researchers can significantly decrease breast cancer metastasis, promoting chronic disease prevention and targeted therapy.  

“The common perception is that the only role of olfactory receptors, which line the nasal cavity and relay sensory data to the brain, is to recognize odor and smell,” director of the Experimental Therapeutics Unit in the Department of Neurology at MGH and senior author of the study, Bakhos Tannous, PhD, said in a press release.  

“Our work suggests that the olfactory receptor 5B21 is also a novel oncogene that may figure prominently in cancer progression by driving breast cancer cells to the brain and other sites in the body.” 

Breast cancer is the second most frequently diagnosed cancer, with more than two million new cases reported each year. However, the migration of breast cancer to the brain is the leading cause of death from the disease. According to the researchers, the data highlights the urgent need for new therapeutic targets to manage or prevent metastasis. 

“The olfactory receptor family of genes is known to be overexpressed in a variety of cancers, including prostate, melanoma, lung, and liver, though its role in breast cancer has been understudied in the past,” said Litia Carvalho, PhD, co-corresponding author of the study and an instructor in Nneurology at MGH. 

Through research with animal models, the team learned that OR5B21 enhances breast cancer cells to metastasize through a signaling pathway that activities the process known as the epithelial to mesenchymal transition (EMT).  

“This activation converts a wide range of extracellular signals into intracellular messages through the signaling pathway NF-κB/STAT, resulting in cell proliferation, invasion and metastasis,” explained lead author Mao Li, a graduate student researcher in the Experimental Therapeutics Unit.  

“Our findings are novel for the field, though further research is needed to determine exactly how OR5B21 induces metastasis.” 

According to the team, future research could lead to a molecular inhibitor of OR5B21 in response to the researcher’s findings that downregulating the olfactory receptor caused a significant decrease in cancer cell metastasis.  

“Our hope is that using OR5B21 as a target for adjuvant therapy could help fill a huge unmet medical need by preventing breast cancer metastasis to the brain and other organs, and thus prolong survival of patients,” Tannous said