Pancreatic cancer remains difficult to
diagnose in its early stages as it is very often asymptomatic. The tumor grows
aggressively and is fairly advanced by the time it is diagnosed clinically. As
a result, prognosis remain poor and nearly 80% of patients diagnosed, rarely live for more than a year following diagnosis.
‘Alterations in pancreatic cancer derived protein, EphA2-EV levels in blood before and after treatment helps in diagnosis and monitoring of the disease.’
Currently surgical resection of the
affected tissue remains the mainstay of treatment but in many cases the tumor
is inoperable due to advanced disease.
This research describes a mechanism by
which it is possible to diagnose pancreatic cancer in its early stages by
measuring the blood levels of a protein EphA2.
This protein is secreted by the tumor and increased levels can be detected in
blood and serves as a biomarker for early diagnosis.
Prior to this research, there have been
no simple methods to isolate and analyze specific extracellular vesicles making
it impossible to use in the diagnostic setting. In addition, the methods used
were not able to reliably distinguish tumor derived EV's from other conditions.
"Pancreatic cancer is one type of
cancer we desperately need an early blood biomarker for," Hu says.
"Other technology has been used for detection, but it doesn't work very
well because of the nature of this cancer. It's really hard to capture an early
diagnostic signal when there are no symptoms. It's not like breast cancer,
where you may feel pain and you can easily check for an abnormal growth."
are Extracellular Vesicles?
vesicles are released from all living cells, prokaryotic as well as eukaryotic,
and resemble the parent cells though they lack the complex internal machinery.
The current research examines a type of EV termed exosomes which measure 50-150
it was thought that extracellular vesicles merely represented cell debris, but
recent studies have shown that they are important structures with a variety of
of Extracellular Vesicles
- Transfer of nucleic acids, lipids and proteins between cells,
causing physiological as well as pathological alterations in both the
parent as well as the target cells.
- Important role in innate and adaptive immunity
- EV's play an important role in the formation and spread of several
cancers including pancreatic cancer.
- Promote development of resistance to anti-cancer drugs by exporting
them away from the tumor site or by neutralizing them.
Extracellular vesicles can be isolated from a wide
range of tissues and body fluids (saliva, blood, urine,
breast milk, seminal, nasal and bronchial lavage and amniotic and fluids)
making them attractive candidates to use as biomarkers in many conditions.
Detection of EV's Using Nanoparticle
In the simple and
rapid technique developed by the research team, a small sample of blood (around
1 microliter), was diluted and applied on a sensor chip coated with antibodies
to an EV membrane protein.
The EV bound to the
chip by antibody was then added to a mixture of antibody coated two types of
nanoparticles, one a red nanorod and the second a green nanosphere. Both these
particles were capable of recognizing a membrane protein EphA2 associated with
Due to the close
contact between the 2 types of nanoparticles on the EphA2 protein, it led to a
coupling effect and change in color and enhancement of the intensity of
refracted light. This is visible as a clear signal when examined using a
Results of the Analysis
The method was able to predict blood samples from
pancreatic cancer with high degree of sensitivity
, including those with
early stage disease. Additionally it was able to distinguish them from samples
patients and healthy individuals.
In addition, as this
method detected slight alterations in
EphA2-EV blood levels in pre- and post-therapy blood samples
potentially be used as a biomarker to monitor response to therapy.
Scope of the Research
- Development of a potential
non-invasive, rapid and reliable method to detect early pancreatic cancer
- Monitoring response to therapy in
- This technique can also be used to
diagnose a wide range of disease conditions by simply customizing the
nanoprobes to EV-specific probes for the condition under investigation.
In fact the research
team employed this method (in a small sample of patients) in cases of active tuberculosis (TB) to detect EV's in
the urine samples
, thereby providing an easy method of diagnosis in those
patients unable to generate sputum. These patients would have had to otherwise
undergo extensive invasive tests for diagnosis.
In conclusion, detection of extracellular
vesicles, once discarded as mere cellular waste is now showing a lot of promise
in the diagnosis and treatment of several diseases. The role of EV's in drug delivery or as therapeutic agents is being
widely investigated by scientists.