First, the APC/CTNNB1 step which leads to a small adenomas.
Second the K-RAS/BRAF step to a large adenoma.
Third, the PIK3CA/PTEN step blocking p53 as well to a cancer.
Fourth, the PRL3 step to metastasis.
The above for the most part are proteins that are blocked, activated, or just disappear or occur. See my review of the nice little book by Bunz. It is worth the read.
This will be very important in staging as well in assessing the early stages of cancer. But the question is how to measure the presence or absence of these proteins to see if the pathways were activated.
Along comes nano technology and a wonderful paper by Stern et al in Nature Nanotechnology which states:
"Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive. However, detecting these biomarkers in physiological fluid samples is difficult because of problems such as biofouling and non-specific binding, and the resulting need to use purified buffers greatly reduces the clinical relevance of these sensors. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. A microfluidic purification chip simultaneously captures multiple biomarkers from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector.... This study marks the first use of label-free nanosensors with physiological solutions, positioning this technology for rapid translation to clinical settings."
Simply the technique used nanotechnology, small nano beads with the ability to have specific protein bind to the surface or lave surface markers activated and then as the nano particles pass through the system they are withdrawn and measured for the presence of the offending proteins or their absence. Brilliant approach and potentially a low cost way to stage and detect cancers.
At the same time in a current paper in Science by Bertotti et al the authors details the pathways and their complexities. They state:
"Tumor onset and progression require the accumulation of many genetic and epigenetic lesions. In some cases, however, cancer cells rely on only one of these lesions to maintain their malignant properties, and this dependence results in tumor regression upon oncogene inactivation ("oncogene addiction"). Determining which nodes of the many networks operative in the transformed phenotype specifically mediate this response to oncogene neutralization is crucial to identifying the vulnerabilities of cancer....We found that Met blockade affected a limited subset of Met downstream signals: Little or no effect was observed for several pathways downstream of Met; instead, only a restricted and pathway-specific signature of transducers and transcriptional effectors downstream of Ras or phosphoinositide 3-kinase (PI3K) was inactivated...Inhibition of Ras-dependent signals and PI3K-dependent signals also resulted in cell-cycle arrest, whereas cells in which Met was inhibited proliferated when Ras or PI3K signaling was active. These findings uncover "dominant" and "recessive" nodes among the numerous oncogenic networks regulated by receptor tyrosine kinases and active in cancer, with the Ras and PI3K pathways as determinants of therapeutic response."
The ability to better understand the pathways and then using nano technology to measure their activation, and then to combine these with sophisticated imaging to localize them allows for both early detection and for the staging of early developmental cancers. The trends presented in these two articles are what I believe are the initial steps which demonstrate true viability of the control of cancer in the early and remediable states.
This approach will, if combined with the multi-modality imaging which is contemporaneously being developed, will permit massive changes in the way we treat disease. Hopefully the new health care bills do not kill things like this. This approach can empower physicians to deal with problems before they become ones requiring hospitals and large institutions. The physicians can become the true police of the body, seeking out the attackers and neutralizing them before any harm is done.
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