Trafficking of Cancer Cells
The trafficking of cancer cells to their final destination may be guided by factors produced by stromal cells of their host organ.
For example, Melanoma cells are closely related to CNS cells. Breast cancer cells more commonly are found in the posterior pituitary. Renal, gastrointestinal and pelvic are cancers tend to metastasize to the cerebellum.
All malignant cells that could evolve will use normal cellular machinery to engage in proliferation and invasiveness. The machinery can be in the malignant cell or its microenvironment, including stromal cells.
Genomic platforms have identified several prognostic and predictive factors, but the comparatively small number of known cellular analytes has limited their broad application.
To address the complexity and reduncancy of cell-death signaling pathways, clinical oncologists have applied the functional profiling platform to select therapies for chemo-naive patients with metastatic cancer.
The funcitonal platform uses morphologic and metabolic endpoints to gauge cellular response to drugs and signal transduction inhibitors in human tumor microspheroids isolated from surgical biopsies.
By examining drug-induced cell death events in native-state microspheroids, the funcitonal profiling platform has the unique capacity to capture stromal, vascular and inflammatory cell interactions with tumor cells, known to be crucial for clinical response prediction.
Citation: J Clin Oncol 27, 2009 (suppl; abstr e15124)
There was a symposium in Washington DC in September of 2009, devoted entirely to the circulating tumor cells (CTC) technology. Although it's a monitoring system to determine if therapy is working, it is not of value in selecting therapy (drug selection).
Circulating tumor cells (CTCs) are cancer cells that have detached from solid tumors and entered the blood stream. This can begin the process of metastasis. To metastasize, or spread cancer to other sites in the body, CTCs travel through the blood and can take root in another tissue or organ.
In stem cell research, anti-cancer treatments often effectively shrink the size of tumors, but some might have the opposite effect, actually expanding the small population of cancer stem cells that then are capable of metastasizing.
The technique requires only a simple blood draw from a patient, but its sensitivity and specificity allow physicians to observe true changes in CTCs that are greater than or less than the 5 CTC cutoff. This information may help physicians predict progression-free and overall survival in individual patients both before and following a single cycle of therapy.
The cutoff is 5 tumor cells. Less than 5 means that things are going well. More than 5 means that things are going poorly. But you can see the difference between 4 and 6 is not all that great. What they found out from that symposium was that it's perhaps useful as an adjunct to traditional methods for following tumor response, such as x-rays, blood tests, CTs, MRIs, history, physical exam, etc.
Basically, CTC labs use "negative selection" to isolate alleged circulating tumor cells. What that means is methods to "selectively" remove circulating normal cells, such as monocytes, lymphocytes, neutrophils, circulating endothelial cells, etc. The problem is that these normal cells outnumber circulating tumor cells by a factor of a million to one, and no "negative selection" procedure (or combination of procedures) can possibly strip away all the normal cells, leaving behind a relatively pure population of tumor cells.
What you have to do is to use a "positive selection" procedure, meaning selectively extracting the tumor cells out of the vastly larger milieu of normal cells. The problem is, when you do this, there is only a teeny tiny yield of tumor cells:
Here's from Wikipedia:
Circulating tumor cells are found in frequencies on the order of 1-10 CTC per mL of whole blood in patients with metastatic disease. For comparison, a mL of blood contains a few million white blood cells and a billion red blood cells.
So, from a typical 7 ml blood draw into a purple top tube, you are going to get, on average, 7 to 70 tumor cells -- total. This may be sufficient for certain molecular type tests (although the degree to which this tiny sample of cells is representative may be questioned), but it isn't nearly sufficient to test even a single drug in a cell culture assay, where one requires millions of cells for quality testing, including requirements for negative and positive controls.
Gregory D. Pawelski
Last edited by gdpawel : 09-21-2012 at 04:40 PM.
Reason: additional info