CASE WESTERN RESERVE (US) — Discovery of a gene variant that drives the spread of breast cancer may pave the way for predicting which patients will develop more aggressive forms of the disease.
“Breast cancer is a genetically complex disease and it remains a challenge to predict disease outcomes and which patients may benefit from more aggressive treatment,” says Goutham Narla, assistant professor at Case Western Reserve School of Medicine.
“Our research has uncovered a promising gene marker that will not only help us better identify tumors that behave badly but provide a basis for developing and personalizing therapies to better treat our patients.”
As reported in the journal Scientific Translational Medicine, researchers discovered that a mutant gene, KLF6-SV1, was linked to the recurrence and metastasis in women with breast cancer. The incorrect splicing of the KLF6 gene essentially creates a protein that causes cancer cells to spread or metastasize.
The researchers examined the tumors of 671 breast-cancer patients in a tumor bank at Erasmus University Medical Center in Rotterdam and found that individuals whose tumors expressed high levels of the gene variant were 50 percent more likely to die.
Since recurrence and metastasis are the major causes of death in breast cancer, this finding will provide a new direction of research to both identify women at risk and to develop targeted drugs that block the process of metastasis.
“This study presents biological proof that this splice variant can potentially be a marker for determining which early stage breast cancer patients will have disease progression,” Narla adds. “More studies need to be done, but this could provide an important prognostic marker to determine which patients need to be treated more aggressively or watched more closely.”
Narla’s laboratory focuses on the identification and characterization of the genes and pathways involved in cancer metastasis. By studying the functional role of the KLF6 tumor suppressor gene, Narla and his team have identified new signaling pathways regulated by this gene family, providing new insight into cancer diagnosis and treatment.
The research shows that KLF6 and FOXO1, both tumor suppressor genes, are turned off as cancer spreads through the body. Since first discovering the KLF6 gene 13 years ago as a medical student at Mount Sinai School of Medicine in the laboratory of Scott Friedman, Narla has been involved in the identification and characterization of the gene and its role in cancer development.
Narla will work with the breast cancer team, led by Lyndsay Harris, to further study KLF6-SV1’s potential as a prognostic marker for patients with poor outcomes. The group also will work to develop novel therapeutics that can turn the protein off and cause the cells to become less aggressive.
The Howard Hughes Medical Institute supported the research.
Source: Case Western Reserve University