Rare HOXB13 African Ancestry-specific Gene Mutation: A Promising Prostate Cancer (PCa) Susceptibility Biomarker

Value Proposition

• Incorporation of the X285K variant of the HOXB13 gene for screening diagnosis or targeted drug discovery will identify and target early-onset and more aggressive prostate cancer disease in higher risk populations.
• No other HOXB13 variant has been found to be preferentially associated with risk for aggressive prostate cancer, making this discovery unique and potentially transformative for precision medicine in prostate cancer.

Unmet Need

• African-American (AA) men face a higher risk of advanced prostate cancer and have nearly double the mortality rate compared to European ancestry men (American Cancer Society, 2021)
• Limited understanding of molecular drivers in African ancestry prostate cancer contributes to health disparities and hinders precision medicine for this high-risk group
• Therefore, there is a strong need to identify genetic drivers of prostate cancer (PCa) among AA populations to inform prostate cancer screening and develop targeted therapies. (European Urology, 2022)

Technology Description

• Researchers at Johns Hopkins have sequenced a large cohort of African-American PCa patients, identifying the novel and recurring X285K variant of the HOXB13 gene, which is linked to early-onset and more aggressive disease manifestation. (British Journal of Cancer, 2021)
• Sequencing and in-vitro studies suggest that HOXB13 X285K is gain-of-function germline mutation and mediates an aggressive prostate cancer phenotype associated with MYC activation and cell-cycle dysregulation (X285K Manuscript).
• These findings may provide biological and clinical rationale to screen men of African ancestry for X285K, and for development of effective treatments for patients carrying this mutation

Stage of Development: The disclosed technology is still in in-vitro studies (the researchers are currently developing an antibody for the variant).

Data Availability: N/a

Publications: : WO 2024/107494