Emory scientists map ‘spiderweb’ of lung cancer proteins to snare new drug targets

cancer
Emory scientists are examining webs of proteins to figure out new ways to target lung-cancer mutations with drugs.

Scientists at Emory University’s Winship Cancer Institute are on a mission to unlock the mysteries of lung cancer cells that have long been thought to be unresponsive to any drug therapy. So they’ve developed what they call a “spiderweb of interactions” between proteins in those cancer cells, and they’re using the data to figure out how to target cancer mutations in the lung.

Using that approach, they discovered that Pfizer’s FDA-approved drug Ibrance (palbociclib), currently used to treat some types of breast cancer, also works against some lung cancer cells carrying a particular mutation. They published their results in Nature Communications. And the drug is now being tested in lung cancer in a clinical trial, according to a press release.

Lead author Haian Fu, Ph.D., and his colleagues developed a method for tagging cancer-associated proteins with two fluorescent molecules and then injecting them into cancer cells. They then observed the interactions between the proteins. Using this method in an initial group of 83 cancer proteins, they discovered 260 interactions that hadn’t been observed before, they say.

One of those newly discovered interactions showed that a gene called LKB1 that’s commonly mutated in lung cancer is connected to CDK4, which is the target of Ibrance. Using genomic analysis and cell culture experiments, Fu and his team showed that cancer cells with defects in LKB1 were sensitive to Ibrance.

Ibrance was the first in a new class of drugs that inhibit proteins called cyclin-dependent kinases (CDKs) 4 and 6. Novartis and Eli Lilly are also working on CDK inhibitors.

Using the new platform developed at Emory, called OncoPPI, the researchers also gathered valuable information about the cancer protein Myc, which is thought to be undruggable. They found an indirect connection between Myc and another protein called Brd4, which is the target of some drugs currently in clinical trials.