good drug results shows power of targeting EGF receptor and HER-2 receptor

good drug results shows power of targeting EGF receptor and HER-2 receptor

There's four epidermal growth factors receptors on cancer cells that are in
the EGF (epidermal growth factor) receptor class of receptors. They are
generally called HER-1, HER-2, HER-3, and HER-4 receptors where the other
name for HER-1 is EGF.

The EGF receptor and HER-2 receptor are believed to be the really dangerous
epidermal growth factor receptors. When they get activated by their
respective growth factors (EGF and HER-2) docking on to the receptor, they
promote a lot of pro-cancer actions by activating either the Akt or ERK
pathway. Both of those pathways probably ultimately activate NF-kappaB (the
NF-kappaB molecule travels from the cytosol to the nucleus and turns on a
whole bunch of procancer genes).

By 1) inhibiting their expression, and 2) blocking EGF and HER-2 from
docking onto the EGF and HER-2 receptors respectively, a powerful anticancer
effect can be obtained. That's how this new drug is apparently working with
good results (it attacks the cancer stem cells). Here's the article that
came out today on it.
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New type of drug shrinks primary breast cancer tumors significantly in just
6 weeks

* w w w .eurekalert.org/bysubject/medicine.php

Public release date: 17-Apr-2008
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Contact: Mary Rice
mary@mrcommunication.org
ECCO-the European CanCer Organisation

New type of drug shrinks 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.

###

Notes for editors: 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.