As the medical community continues to make positive strides in personalized
cancer therapy, scientists know some dead ends are unavoidable. Drugs that target
specific genes in cancerous cells are effective, but not all proteins are
targetable. In fact, it has been estimated that as few as 10% to 15% of human
proteins are potentially targetable by drugs. For this reason, Georgia Institute
of Technology researchers are focusing on ways to fight cancer by attacking
defective genes before they are able to make proteins.
Professor John McDonald is studying micro RNAs (miRNAs), a class of small
RNAs that interact with messenger RNAs (mRNAs) that have been linked to a
number of diseases, including cancer. McDonald’s laboratory placed two
different miRNAs (MiR-7 and MiR-128) into ovarian cancer cells and watched how
they affected the gene system. The findings are published in BMC Medical Genomics.
“Each inserted miRNA created hundreds of thousands of gene expression changes,
but only about 20% of them were caused by direct interactions with mRNAs,” said
McDonald. “The majority of the changes were indirect—they occurred downstream
and were consequences of the initial reactions.”
McDonald initially wondered if those secondary interactions could be a
setback for the potential use of miRNAs, because most of them changed the gene
expressions of something other than the intended targets. However, McDonald
noticed that most of what changed downstream was functionally coordinated.
miR-7 transfection most significantly affected the pathways involved with
cell adhesion, epithelial-mesenchymal transitions (EMT), and other processes
linked with cancer metastasis. The pathways most often affected by miR-128
transfection were different. They were more related to cell cycle control and
processes involved with cellular replication—another process that is overactive
in cancer cells.
“miRNAs have evolved for millions of years in order to coordinately regulate
hundreds to thousands of genes together on the cellular level,” said McDonald. “If we can understand which miRNAs affect which suites of genes and their
coordinated functions, it could allow clinicians to attack cancer cells on a
systems level, rather than going after genes individually.”
Clinical trials for miRNAs are just beginning to be explored, but definitive
findings are likely still years away because there are hundreds of miRNAs whose
cellular functions must be fully understood. Another challenge facing
scientists is developing ways to effectively target therapeutic miRNAs to
cancer cells, something McDonald and his Georgia Tech peers are also
investigating.
Source: Georgia Institute of Technology