Lapatinib shrinks primary breast cancer tumours significantly in just six weeks

17 Apr 2008

Cancer stem cells new target for research and treatment

A small scale trial of lapatinib, which targets cell surface receptors to regress tumours, has given remarkable results after just six weeks of use, it was announced at the 6th European Breast Cancer Conference in Berlin today.

The research has demonstrated for the first time that the tyrosine kinase inhibitor lapatinib can decrease tumour-causing breast cancer stem cells in women receiving pre-op treatment.

Dr. Angel Rodriguez, from the Lester and Sue Smith Breast Centre, Baylor College of Medicine, Houston, USA, studied 45 patients with locally advanced breast cancer who had higher than normal levels of the gene HER-2 (worldwide one in five cases of breast cancer).

The patients received lapatinib for six weeks, followed by a combination of weekly trastuzumab and three-weekly docetaxel, given over 12 weeks, before primary surgery. Biopsies were performed at the time of diagnosis and also after six weeks of lapatinib and cells from the tumours were obtained and analysed.

"We saw significant tumour regression after six weeks of just lapatinib," said Dr. Rodriguez, "tumour measurements showed a decrease of 60.8%." The team had already established that standard pre-op chemotherapy actually increased the number of breast cancer stem cells*, so were pleased to discover that lapatinib did the opposite.

The results suggest that specifically inhibiting the pathways responsible for stem cell self-renewal using drugs such as lapatinib could provide a possible therapy for eliminating cancer stem cells in order to achieve long-term eradication.

Cancer stem cells regenerate the tumour after attack from chemotherapy drugs, maintaining the malignant tissue. "This indicates that the stem cells themselves should be the specific target of chemotherapy drugs," said Dr. Rodriguez. "Rather than the broad brush approach, in which cells are killed indiscriminately, targeting the stem cells may be more effective and also prevent some of the unpleasant side effects associated with conventional chemotherapy treatment."

Scientists believe that cancer stem cells, which form about 10% of the tumour, come into being through damage to their own DNA, affecting the regulation of their self-renewal.

While other cells divide into two ‘daughter' cells, a stem cell can divide into a new stem cell and a ‘progenitor' cell. This progenitor cell loses the power of self-renewal, but changes into the cell type of the tissue served by the stem cell, in this case the tumour. The stem cell population then continues to renew itself as it generates new cells for the tissue. "This means that, unlike other cells, the stem cell has lost control over its own population size," said Dr. Rodriguez. Lapatinib has few side effects, and those that exist are minimal, including diarrhoea and acne. But it is expensive, costing between $2000 and $3000 a month.

 "It must be stressed that though this is an exciting finding, it can only apply to the one in five breast cancer sufferers who over express HER-2, and the trial is so far very small", added conference chair Professor Emeil Rutgers of the Netherlands Cancer Institute.

Dr. Rodriguez continued: "We will be starting further studies on stem cells in order to confirm [the findings]. We will also look into the applicability of testing novel agents targeting tumour-initiating cells. This finding should also apply to other types of cancers and research of tumour-initiating stem cells in other cancers is ongoing." The problem arises in identifying the cancer stem cells, which can currently only be assessed by their effects rather than their physical characteristics.

"International studies are currently underway looking at