Study demonstrates drug's effect on breast cancer stem cells
When used in combination with traditional chemotherapy, new 'targeted' therapies don't just kill 'normal' cancer cells, but appear to be able to target the cancer 'stem cells' from which tumour cells develop, stopping the cancer from returning, scientists have found.
The discovery, by researchers at the Baylor College of Medicine in Houston, suggests that new combinations of drugs can be used to target the very root of the disease.
The finding also helps explain why new targeted therapies like lapatinib (Tykerb) and trastuzamab (Herceptin) can be effective at preventing cancer from coming back.
Dr Michael Lewis, assistant professor of molecular and cellular biology, likened the process to treating weeds. He said: "It's not enough to kill the dandelion blossom and stalk that appear above ground. You have to kill the root beneath the soil as well."
Dr Lewis's study, which is published in the Journal of the National Cancer Institute, may explain why chemotherapy sometimes does not work.
"It appears that these (cancer stem) cells, by their nature, are resistant to the effects of anti-cancer drugs. However, treatment with the drug lapatinib and anti-cancer drugs appears to kill both the tumour and the stem cells, reducing the threat of relapse in patients whose tumours carry a protein marker called HER2," he revealed.
The researchers' findings are based on a study of tumour biopsies from breast cancer patients, both before and after treatment.
Thirty-one patients had tumours that lacked the HER2 protein marker and these patients were treated with conventional chemotherapy.
A further 21 patients had HER2-positive tumours, and these were treated with lapatinib and two other breast cancer drugs.
The scientists estimated the percentage of stem cells in each biopsy by staining the samples to highlight these cells.
They found that in biopsies treated with conventional chemotherapy, the number of tumour cells decreased but the proportion of cancer stem cells to tumour cells was higher than before treatment, indicating that the treatment killed the tumour cells but not the cancer stem cells.
However, in biopsies treated with lapatinib, the proportion of stem cells relative to tumour cells did not change and, in some cases, fell. These patients' tumours also shrank more than those of patients treated with standard chemotherapy.
Dr Jenny Chang, associate professor of medicine at Baylor and medical director of the college's Breast Care Cancer Centre, said that the tumours shrank dramatically when treated with a combination of lapatinib and chemotherapy.
"But in contrast to treatment with conventional chemotherapy, the relative proportion of stem cells did not go up. This means the stem cells were killed off with the same frequency as the bulk of the tumour. This is the first time this has been demonstrated," she added.