Tuesday, April 9, 2013

An Interesting New Cancer Technology

The challenge is determining of a cancer has metastasized is to find out where and how much. The classic approach is to look at the local draining lymph nodes and see if has gone there. However the cancer cells may often escape through the blood system and not the lymph system. Consider ocular melanoma, there is no lymph system connection and it spreads by hematological means only.

That means that by examining the blood we should be able to find the wandering malignant cells, at least in theory. In a recent release by MedGadget the article relates developments at MGH in Boston as follows:

Circulating tumor cells (CTCs) are shed by primary tumors and allow the cancer to metastasize to the distant sites. While this is a devastating tool in cancer’s war chest, it offers clinicians a marker through which to diagnose and monitor progress of the disease. Since the discovery of CTCs over a hundred years ago, researchers have been developing ever more sensitive methods of capturing them since they’re extremely rare in whole blood.

In a recent development by Ozkumur et al at MGH the authors state:

Circulating tumor cells (CTCs) are shed into the bloodstream from primary and metastatic tumor deposits. Their isolation and analysis hold great promise for the early detection of invasive cancer and the management of advanced disease, but technological hurdles have limited their broad clinical utility. We describe an inertial focusing–enhanced microfluidic CTC capture platform, termed “CTC-iChip,” that is capable of sorting rare CTCs from whole blood at 107 cells/s. 

Most importantly, the iChip is capable of isolating CTCs using strategies that are either dependent or independent of tumor membrane epitopes, and thus applicable to virtually all cancers. We specifically demonstrate the use of the iChip in an expanded set of both epithelial and nonepithelial cancers including lung, prostate, pancreas, breast, and melanoma. 

The sorting of CTCs as unfixed cells in solution allows for the application of high-quality clinically standardized morphological and immunohistochemical analyses, as well as RNA-based single-cell molecular characterization. The combination of an unbiased, broadly applicable, high-throughput, and automatable rare cell sorting technology with generally accepted molecular assays and cytology standards will enable the integration of CTC-based diagnostics into the clinical management of cancer. 

There are several problems here however:

1. As we had demonstrated in some of our prior analysis, blood borne cancer cells are rare, but more importantly they are cells which are coming from and going to organs. Namely they are in transit, from whence and to where we do not know.

2. The genetic states of each of these wandering cells may be a marker of from whence it came. The problem is that we do not fully understand this genetic mutation process, and in fact as we have shown before it may actually be a Markov like chain process.

3. Understanding this change in cells may be of significant therapeutic value. However this again is uncertain given our current state of knowledge.

4. Again we come back to the cancer stem cell and ask if the few cells we find in the blood stream are the right cells to examine.

However this advance could provide significant data to allow us to expand the understanding of mutating cancer cells.


Ozkumur, E.,Inertial Focusing for Tumor Antigen–Dependent and –Independent Sorting of Rare Circulating Tumor Cells, Sci Transl Med Vol. 5, Issue 179, p. 179