A novel type of drug can shrink primary breast cancer tumors significantly in just 6 weeks Research provides leads to a new target in cancer treatment -the cancer stem cell.

(Berlin, Germany) A drug that targets the cell surface receptors that play an important role in many types of cancer can bring about significant tumour regression in breast cancer after only six weeks of use, a scientist told the 6th European Breast Cancer Conference (EBCC-6) today (Thursday 17 April).  Dr. Angel Rodriguez, from the Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA, said that the work demonstrated for the first time that the tyrosine kinase inhibitor lapatinib could decrease tumour-causing breast cancer stem cells in the primary breast cancers of women receiving neoadjuvant treatment (treatment given before the primary surgery for the disease).

Dr. Rodriguez and colleagues studied 45 patients with locally advanced breast cancer in which the gene HER-2 was over-expressed.  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 analyzed.

“We saw significant tumour regression after six weeks of single agent lapatinib,” said Dr. Rodriguez.  “Bi-dimensional tumour measurements showed a median decrease of minus 60.8%. We had previously showed that tumour-causing breast cancer stem cells were resistant to conventional preoperative chemotherapy; indeed, residual cancers that were exposed to such chemotherapy showed an increase in tumour-causing cells and enhanced tumour initiation by the formation of mammospheres, small tumours that form when tumour-causing cells are cultured in a test tube, which reflect the capacity of the cells to self-renew.  So we were excited to see that the results with lapatinib were different.”

Dr. Rodriguez’s results suggest that specific signalling inhibitors of the pathways responsible for stem cell self-renewal could provide a possible therapy for eliminating tumour-causing cells in order to achieve the long-term eradication of cancer.

Cancer stem cells help maintain the malignant tissue in the tumour by regenerating the tumour after attack from chemotherapy drugs.  “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 come into being through damage to their own DNA, which affects the regulation of their self-renewal.  Other cells divide into two ‘daughter’ cells, but a stem cell can divide into a new stem cell and a ‘progenitor’ cell.  The progenitor cell loses the power of self-renewal, but can still change into the cell type of the tissue served by the stem cell.  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.  “In the US it costs between $2000 and $3000 a month,” he said.

“This is an exciting finding, and we will be starting further studies on stem cells in order to confirm it.  We will also look into its applicability in 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,” said Dr. Rodriguez.

“International studies are currently underway looking at the effect of lapatinib in lung, colon, head and neck, gastric, oesophageal, and bladder cancer and lymphoma, among others,” he said.

Note:  Lapatinib has not yet been licensed for use in the EU, although it has been approved in Switzerland and received a positive opinion regarding a conditional marketing authorisation from the European Medicines Agency in December.  This conditional authorisation refers to its use in patients with advanced or metastatic breast cancer with HER-2 over-expression in the tumours.

Catalogue no: 204, Thursday 18 April, 17.15 hrs CEST (Hall 1)

A team of researchers at Yale School of Medicine have identified, characterized and cloned ovarian cancer stem cells and have shown that these stem cells may be the source of ovarian cancer’s recurrence and its resistance to chemotherapy.

“These results bring us closer to more effective and targeted treatment for epithelial ovarian cancer, one of the most lethal forms of cancer,” said Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.

Mor presented his findings recently at the annual meeting of the American Association for Cancer Research (AACR) Meeting in San Diego, California.

Cancerous tumors are made up of cells that are both cancerous and non-cancerous.  Within cancerous cells, there is a further subclass referred to as cancer stem cells, which can replicate indefinitely.

“Present chemotherapy modalities eliminate the bulk of the tumor cells, but cannot eliminate a core of these cancer stem cells that have a high capacity for renewal,” said Mor, who is also a member of the Yale Cancer Center.  “Identification of these cells, as we have done here, is the first step in the development of therapeutic modalities.”

Mor and colleagues isolated cells from 80 human samples of either peritoneal fluid or solid tumors.  The cancer stem cells that were identified were positive for traditional cancer stem cell markers including CD44 and MyD88.  These cells also showed a high capacity for repair and self-renewal.

The isolated cells formed tumors 100 percent of the time.  Within those tumors, 10 percent of the cells were positive for cancer stem cell marker CD44, while 90 percent were CD44 negative.

Mor and his team were able to isolate and clone the ovarian cancer stem cells.  They found that these cells were highly resistant to conventional chemotherapy while the non-cancer stem cells responded to treatment.  “Isolating and cloning these cells will lead to development of new treatments to target and eliminate the cancer stem cells and hopefully prevent recurrence,” said Mor.