Wednesday, April 30, 2008

Eradicating stem cells in breast cancer

Results from a small clinical trial of 45 patients with locally advanced breast cancer suggests that the novel agent lapatinib (Tykerb, GlaxoSmithKline) has an effect on tumour-causing breast cancer stem cells. Lapatinib is approved to treat breast cancer that has metastasized and contains the protein marker called HER-2 in the US, but not the EU.

Chemotherapy can remove breast cancer tumours, but it often fails to root out the stem cells that can revive the cancer.

Comparing the challenge to eradicating stubborn weeds from a garden, the researchers at Baylor in Houston, Texas, said chemotherapy often fails because it leaves behind many of the stem cells that lead to recurrence.

Think of it this way: 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. The finding underscores the need to develop a treatment that can target stem cells in addition to the tumour itself. It appears that these cells, by their nature, are often resistant to the effects of anti-cancer drugs.

A cocktail of chemotherapy, together with the drug lapatinib, appears to kill both the tumour and the stem cells (6th European Breast Cancer Conference (EBCC): Abstract 204).

The Baylor researchers took biopsies from tumours of the patients with, and without, the HER-2 marker before and after different treatments. In the group of people whose tumours did not carry the HER-2 marker, the 31 patients received conventional chemotherapy. While the number of tumors significantly decreased, the proportion of cancer stem cells was greater than before the treatment.

The other group were given lapatinib and two common breast cancer chemotherapy drugs. That group saw a dramatic drop in tumour cells, and the percentage of cancer stem cells remained unchanged or even dropped slightly, but the tumour shrank dramatically. In contrast to treatment with conventional chemotherapy, the relative proportion of stem cells did not go up. The stem cells were, therefore, killed off with the same frequency as the bulk of the tumour.

This is the first time this has been demonstrated and offers an insight to developing new treatment strategies for fighting cancer in the future.

Source: Journal of Nat Cancer Institute

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