Cancer cells not “addicted to MELK”
Gene editing technology suggests that a cancer drug in on-going clinical trials hits a different target than previously thought.
Like a person who is dependent on coffee to be productive, cancer cells are dependent on the products of certain genes in order to dominate their environment and grow. Cancer cells will stop growing and die when the activity of these gene products is blocked. These genes are known as cancer dependencies or “addictions”. As a result, researchers are constantly looking for cancer dependencies and developing drugs to block their activity.
It was previously believed that a gene called MELK was an addiction in certain types of breast cancer. In fact, pharmaceutical companies had developed a drug to block the activity of MELK, and this drug is currently being tested in human patients. However, Ann Lin, Christopher Giuliano and colleagues have now taken a second look at the role of MELK in breast cancer, and have come to a different conclusion.
Using a gene editing technology called CRISPR/Cas9, Lin, Giuliano and colleagues removed MELK activity from several cancer cell lines (cancer cells that keep dividing and growing over time, under certain conditions in a laboratory.). This did not stop cancer cells from multiplying, suggesting that MELK is not actually a cancer addiction.
Additionally, when breast cancer cells that do not produce MELK were exposed to the drug that is supposed to block MELK activity, the drug still stopped cell growth. Since the drug works when MELK is not present in the cell, the drug must be binding to other proteins. This suggests that MELK is not the actual target of the drug.
Lin, Giuliano and colleauges suggest that, in the future, CRISPR/Cas9 technology could be used to better identify cancer dependencies and drug targets before cancer drugs are given to human patients.
To find out more
Read the eLife research paper on which this eLife digest is based: “CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials” (March 24, 2017).