Antimicrobial resistance in disease-causing microbes has garnered
attention in recent years, but another persistent area of drug resistance is
the ability for tumors to evade chemotherapy drugs. Methotrexate is one of the
oldest chemotherapy agents, and although it can be quite effective against many
types of cancer and other conditions, in many cases it stops working because
the patient becomes resistant to the drug's effects.
In a new study, researchers have developed a rapid, low-cost screening
method to decipher the gene mutations behind drug resistance. They used baker's
yeast to test the technique in the context of methotrexate resistance and identified
10 mutations that can confer resistance to the drug, offering potential new
leads that could help scientists make the drug more reliable.
The research was led by postdoctoral fellow Lai Wong in the lab of Guri
Giaever and Corey Nislow at the University of British Columbia, along with
collaborator Pat Flaherty from the University of Massachusetts, Amherst. The
method they developed is a "back-to-the-future" approach that
combines a traditional screening approach for identifying sources of drug resistance
with newer techniques of "massively parallel" and "deep"
genetic sequencing, along with advanced statistical algorithms. The method is a
significant improvement over existing techniques to understand the genetic
mutations relevant to drug resistance.
The technique's success in identifying methotrexate resistance mutations
demonstrates its potential uses for understanding not only the mechanisms
behind resistance for this important chemotherapy agent, but potentially for
many other drugs as well.
Posted by Dr. Tim Sandle