Scientists are beginning to discover myriad strategies tumors use to avoid attacks by anti-cancer drugs.

When cancer cells are first discovered, many drugs can blast them into oblivion. But over time, cancers begin to withstand those first line drugs and continue to grow and spread.

“If you already have 1010 tumor cells, the chances are you’re going to have some kind of resistance develop,” said William Pao, a physician scientist at Vanderbilt University, who first uncovered mechanisms of drug resistance in lung cancer. “Even if you kill 99.9 percent of cells you’re still left with a ton of cells which then can start to grow.”

A long-standing hurdle in cancer therapy, researchers are now making inroads into understanding how cancer cells acquire drug resistance, and they’re finding that genetic mutations are just one of many strategies cancers use to evade death. Cancer cells have been found to boost transcription of survival genes, drill out the cores of transport proteins, or even employ alternate protein configurations to avoid extinction. While researchers are learning to apply the findings to overcome specific types of drug resistance, it’s quickly becoming clear that there is no single pathway tumors use to avoid cancer drugs, and that the problem of cancer resistance is far from over.