The research study on the use of ISET by Rarecells to diagnose and treat lung cancer at the first signs of tumor growth, “Sentinel Circulating Tumor Cells Allow Early Diagnosis of Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease,” is in the Top 10 of most viewed research papers at the Public Library of Science (PLOS) ONE open-access journal.
According to Raymond Barnhill, MD, Adjunct Professor of Pathology at UCLA’s David Geffen School of Medicine and Professor of Pathology at Curie Institute Paris, there is quite a bit of excitement around the paper because it holds the promise for early intervention into multiple tumor types.
“This is a highly innovative blood filtration method to test for not only lung cancers, but all solid tumors at their earliest stages of development when they are simply not otherwise detectable with current technology,” said Dr. Barnhill.
Lung cancer, as well as ovarian, colon, pancreatic and breast cancers—all of which are the most deadly tumors—grow so silently that they typically are not diagnosed until they have spread to other locations in the body. By the time they are detected, the cancer is essentially incurable. It’s a great uphill battle to try to contain tumors at that stage.
“By the time these tumors are detected, they are essentially incurable,” said Dr. Barnhill. “Unfortunately, it’s a great uphill battle to try to contain tumors at stages III and IV. I think this is what’s so encouraging about the ISET study: this technology is applicable to all solid cancers, which is tremendously promising.”
Another reason Barnhill believes the research is significant is the mechanics of the ISET circulating tumor cell (CTC) isolation. Most other CTC isolation techniques rely on the expression of certain cell surface features—or antigens—that are supposed to be unique to cancerous cells. These systems isolate CTCs that express these antigens using antibodies that bind these antigens, but this creates a risk for false negative results and false positive results because no universal antibody to detect all the variety of CTCs is available.
As discussed in an earlier blog post (http://www.isetbyrarecells.com/sentinel-cells-the-early-clues-to-silent-tumors/), CTCs are cells in transition. In order to leave the original tumor and enter the bloodstream, they go through the epithelial-mesenchymal transition (EMT) which allows them to change from tightly packed epithelial cells to migratory mesenchymal cells. This is a vital step in metastasis. CTCs are very heterogeneous cells—some express the targeted surface antigens while others do not.
Since tumor cells are typically twice normal size, ISET (Isolation by Size of Tumor/Trophoblastic Cells) selects likely CTCs by size alone. Eliminating white blood cells through the pores of the filter, ISET filtration allows to extract from blood unusually large cells, with are then confirmed as cancerous with cytopathological analysis. Only large cells which demonstrate cancerous properties are determined to be cytopathologically validated CTCs, or CCCs.
The ISET process has proven to detect more CTCs with greater sensitivity than methods that rely on the expression of discrete tumor cell antigens. ISET also has far fewer false negative results than antigen-based tests and the morphology-based enrichment technique used by ISET is able to find more efficiently cancerous microemboli, or the clusters of cells often formed by CTCs in circulation. (A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas; Br J Cancer; Sep 6, 2011; 105(6): 847–853.)