Consider that cancer is basically a disease of altered proteomics
(proteins), where deranged, hyperactive, or dominating protein signal
pathways may drive cancer survival, growth, invasion, and
metastasis. Pathogenic alternations in protein networks extend outside the cancer cell to the tissue microenvironment, in which exchange of cytokines, enzymes, enzyme inhibitors, motility factors, and adhesion molecules act to the advantage of the tumour cell.
Smart particles of polymer gel that can therefore sieve rare proteins from the
blood could allow cancer to be diagnosed at an earlier stage. Researchers
looking for ways to make earlier diagnoses of cancer have been concentrating
on finding new biomarkers or molecules indicating the presence of
tumours before any symptoms show.
Among the top candidates are small proteins that tumours release into the blood. The trouble is that these are present in only minute quantities and so get masked by larger, more
common blood proteins, such as albumin. It is possible to strip
the larger proteins from blood samples, but this tends to remove
biomarkers as well, because they often bind to the larger proteins. The
particles, about 1 micrometre in diameter, solve the problem by
removing a particular biomarker from blood, and leaving any large
proteins behind. They do this because they can be "baited" with
different chemicals that allow them to trap only certain types of
Scientists at George Mason University have been working on refining the technology. They have developed techniques using protein gels consisting of hydrogel particles. These hydrogel particles, combined with the use of mass spectrometry to isolate the aberrant proteins being pumped out by the tumour at an early stage, may help to identify either early tumour proliferation or progression.
Last year, the group showed that their baited particles selectively pulled small
proteins out of test solutions (Nano Letters, DOI:
Now they have used the nanoparticles to extract a known cancer biomarker
from samples of blood serum and have proven the concept.
the American Association for Cancer Research meeting last week, Luchini described how the researchers spiked
serum with traces of platelet-derived growth factor (PDGF), bound to
albumin. PDGF is a biomarker associated with growth of the blood
vessels that feed a developing tumour. The hydrogel particles removed
the biomarker from its albumin carrier and concentrated it from levels that were
previously below the limits of detection. The particles also protected
PDGF from attack by a protein-digesting enzyme, which is important
because blood contains similar enzymes.
The ultimate payoff of clinical proteomics will be to go beyond molecular discovery to reach individualised therapy. Just as patients visiting an oncologist’s office are distinct individuals, with no two being exactly alike, it is likely that their respective tumours have unique molecular patterns, even though they may be given the same pathological description. Individualised therapy in this concept would mean treating patients by the particular mutations, or protein aberrations that their tumour expresses, with the goal of having appropriate therapy which offers the most optimised response.