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New type of drug shrinks primary breast cancer tumors significantly in just 6 weeks
April 17, 2008Research 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.
ECCO-the European CanCer Organisation
"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.
ECCO-the European CanCer Organisation
Stem Cell Current Events and Stem Cell News RSSFirst reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
Researchers find potential treatment for Huntington's disease
Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease.
Researchers 'notch' a victory toward new kind of cancer drug
Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed.
UCI embryonic stem cell therapy restores walking ability in rats with neck injuries
The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.
First use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
Immune therapy can protect against or treat later lymphoma
Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection.
Immunotherapy demonstrates long-term success in treating lymphoma
Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT).
Of mice and men: Stem cells and ethical uncertainties
The recent creation of live mice from induced pluripotent stem cells (iPSCs) not only represents a remarkable scientific achievement, but also raises important issues, according to bioethicists at The Johns Hopkins University's Berman Institute of Bioethics.
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