- When cancer cells or microorganisms, such as bacteria or viruses, don’t respond to a drug that is usually able to kill or weaken them. Drug resistance may be present before treatment is given or may occur during or after treatment with the drug. In cancer treatment, there are many things that may cause resistance to anticancer drugs. For example, DNA changes or other genetic changes may change the way the drug gets into the cancer cells or the way the drug is broken down within the cancer cells. Drug resistance can lead to cancer treatment not working or to the cancer coming back.