Studying Signaling Pathways May Lead to New Targeted Prostate Cancer Treatments

Researchers at Florida State University (FSU) are now reporting in the latest issue of PLOS One, that by looking at altered signal genetic pathways, it may be possible to come up with new, more targeted prostate cancer treatments.  

The researchers theorized that by looking just at individual genes and targeting those specific mutations, clinicians may have been receiving a less than full picture.  So they decided to focus on pathways and conducted a Gene Set Enrichment Analysis along with a Signaling Pathway Impact Analysis.

Although genetic profiles vary from patient to patient, the authors hypothesized that genetic changes should converge at the pathway level. They report the alteration of the transforming growth factor-beta (TGF-β) signaling pathway in prostate cancer. They also found that regulation by the protein “Ran” may be involved in the formation pathway in prostate cancer.

Study co-author Jennifer Myers, who is a graduate student in the FSU Department of Chemistry and Biochemistry, said because genes work in concerted networks to exert their molecular effects, changes in gene expression should be indicative of altered pathways. “By looking for altered pathways, we’ve significantly increased the size of our target,” said Myers in a FSU news release .

The team notes that the TGF-β pathway has been extensively studied in prostate cancer. However, they believe that the Ran/mitotic spindle pathway and the role of Ran overexpression in prostate cancer until now has not been investigated. Myers said the next step will be to confirm the significance of the Ran/mitotic spindle pathway in prostate cancer.

The Florida investigators utilized next-generation genome sequencing data from The Cancer Genome Atlas. The team assessed differential gene expression between age-matched and stage-matched human prostate tumors and nonmalignant samples in order to craft a pathway signature of prostate cancer. Up-regulated and down-regulated genes were assigned to pathways composed of curated groups of related genes, according to the researchers. They also found that several other significant pathways are involved, suggesting “actin cytoskeleton regulation, cell cycle, MAPK signaling, and calcium signaling” may be altered in prostate cancer.

The investigators contend that there may significant value in a pathway-based genetic analysis.  They believe that further pathway-based genetic analysis studies may lead to new targeted therapies for prostate cancer.

Currently, prostate cancer is the second most diagnosed cancer among American men, according to the American Cancer Society.