On Cancer: Study Reveals How Some Breast Cancers Become Resistant to Targeted Drugs

By Julie Grisham, MS, Science Writer/Editor  |  Monday, November 17, 2014 – For people with advanced breast cancer, several clinical trials have shown that experimental targeted drugs called PI3K inhibitors can temporarily halt the spread of disease. But eventually the tumors learn to outwit the drugs and begin growing again.

Now a team of researchers from Memorial Sloan Kettering and elsewhere has gained new insights into how tumors develop resistance to these drugs. The findings suggest that adding additional drugs to the treatment regimen may provide a longer-lasting response and a greater benefit to patients.

“These targeted drugs are already achieving an unprecedented response in patients with metastatic disease who have stopped responding to chemotherapy and hormone therapy,” says Maurizio Scaltriti, a cancer biologist who is co-director of the laboratory of MSK Physician-in-Chief José Baselga and senior author of a study published today in Nature. “Now that we understand how resistance evolves in breast tumors, we can propose new therapeutic strategies for these patients.”

A Comprehensive, In-Depth Analysis

Ongoing efforts to sequence tumors’ genomes are providing a previously unimaginable level of detail about how cancers develop.

In the current study, the investigators began by analyzing 14 metastatic tumors from a single patient who had recently died from breast cancer. The patient’s cancer initially tested positive for mutations in a gene called PIK3CA. Based on that result, she enrolled in a clinical trial testing the drug BYL719, a PI3K inhibitor, which successfully controlled her cancer for many months. Eventually, however, the drug stopped working, and she died.

Soon after, all of the patient’s tumors were analyzed using a technology developed at MSK called MSK-IMPACTTM, which enables investigators to look at hundreds of genes and to collect an enormous amount of information about each of them. One of the lead developers of the technology, MSK genomics researcher Michael Berger, was a co-author on the Nature study.