Indo-US team discovers therapy for pancreatic cancer

Sridhar Krishnaswami
Washington, Dec 30 (PTI) A joint Indo-US team of
scientists have discovered a new way of treating pancreatic
cancer by identifying a receptor whose activation may be
responsible for some types of the disease.

The team of scientists from Johns Hopkins Kimmel Cancer
Center in Baltimore, Maryland, and Institute of Bioinformatics
in Bangalore identified a receptor called phosphorylated
epidermal growth factor receptor (pEGFR), whose activation may
be responsible for some pancreatic cancers.

The new personalised therapy involves targeting the
receptor, which is the activated form of a protein that binds
to Epidermal Growth Factor (EGF), which promotes cell growth
and differentiation.

When EGF attaches to EGFR, it activates it as a tyrosine
kinase enzyme, triggering reactions that cause cells to grow
and multiply, a press release by the Johns Hopkins Kimmel
Cancer Center stated.

EGFR is found at abnormally high levels on the surface
of many types of cancer cells, which may divide excessively in
the presence of EGF, it said.

In a new study, published online in the Journal of
Proteome Research, the researchers suggest that physicians
potentially could test patients for signs of pEGFR, then
direct therapies such as EGFR inhibitors directly at the
signal pathway its part of to shrink or prevent pancreatic
tumors.

"EGFR inhibitors and other targeted cancer therapies
that interfere with specific molecules involved in cancer
development so far have had limited success clinically, but
that may be because scientists are not hitting the correct
molecular target or applying them to all patients, senior
study author Akilesh Das said.

He said "you can’t do targeted therapy without knowing
that you have the right target. We propose that the use of
activated EGFR as a predictive tool for clinical response to
EGFR inhibitors could lead to an improved outcome of clinical
trials while sparing the large majority of the patients who
might not benefit from these drugs.

The release has pointed out that for the study, Pandey
and colleagues first analyzed a series of pancreatic cell
lines, looking for tyrosine kinase activity, finding that
cells derived from one particular patient showed dramatic
response.

Next, they studied these cells in greater detail using
quantitative mass spectrometry, finding within the activated
tyrosine kinase pathways an unusual activation of the EGFR
pathway.

To test whether EGFR signaling was responsible for cell
proliferation in the P196 cell line, researchers injected mice
with cells from P196 and other pancreatic cell lines to grow
tumors, then treated the mice with erlotinib, a drug that
inhibits EGFR.

The drug made a dramatic difference in tumors from the
cell lines that showed activation of EGFR, shrinking them
almost entirely, but had no effect on tumors grown from cell
lines that did not show activation of EGFR.

In additional experiments, the scientists used a
technique called immunohistochemical labeling to study
sections of tumor tissue, looking for presence of pEGFR.

While the sections of untreated tumors showed intense
staining for pEGFR, the erlotinib-treated tumors showed no
labeling, an indication that the drug had turned off the EGFR
signal.

"By combining proteomic analysis with
immunohistochemistry, we have shown EGFR as a novel target in
a subset of pancreatic cancers," Pandey added.

"Three of three tumors that responded to erlotinib
stained positive for pEGFR, as compared with zero of 11 that
did not. This indicates pEGFR positivity is significantly
associated with erlotinib sensitivity and could be used as an
efficient screening tool to select patients who are more
likely to respond to EGFR inhibitors, he added. PTI