Here’s Why Some Cancer Is Resistant to Drugs

Cancer is insidious in so many ways, not the least of which is its ability to mutate constantly and keep growing, even when hit with powerful chemotherapy drugs. Now researchers have carefully canvassed the genomes of some tumors and revealed some of those cancers’ secrets to survival.

Neville Sanjana from the New York Genome Center and New York University and his team took advantage of a new technology called CRISPR to precisely edit the genomes of tumors. They wanted to cut out specific parts of the genome to see if they affected the way the cancer grew. Instead of focusing on known cancer genes, however, they concentrated their splicing efforts on the so-called non-coding parts of the genome: the 98% that doesn’t correspond to known genes. Until recently, scientists called this part of the genome junk DNA, assuming it wasn’t critical to how genes function. But they’ve come to understand that these sections of DNA are essential to how genes work, similar to role that directors and producers play in a movie: they aren’t visible, but they’re guiding the action. The non-coding areas are providing important instructions to genes for when to be active and how much protein to produce.

“This is 98% of the genome and an area a lot of scientists believe we need to look very carefully at,” says Sanjana. “The genome is like a piece of text—if we don’t have Microsoft Word to cut, copy and paste, it’s hard to manipulate the text. Only recently have we had tools like CRISPR to write and edit this text.”

By selectively and methodically editing out specific sections of the genome from a line of human melanoma cells taken from a patient, and then exposing them to a commonly used anti-cancer drug, Sanjana found which parts were contributing to the tumors’ resistance to the drug. In a report published in the journal Science, they even identified some specific regions that could be immediately helpful in identifying people who might develop resistance to the drug and who might benefit from a combination therapy in order to give them better responses. The information could also be invaluable in creating new drugs. Now, with the additional information from the non-coding regions of the genome, scientists will have far more targets for developing possible drugs.