New Assay for Circulating Tumor Stem Cells May Be Game Changer

Zosia Chustecka

April 05, 2011

April 5, 2011 — Although there has been some excitement over the potential clinical applications of measuring circulating tumor cells (CTC) from the blood of patients with cancer, one of the problems has been a lack of specificity in the assays that are available.

However, a new assay that homes in on cancer stem-like cells — although not yet ready for clinical use — offers hope for this approach, according to an editorial published online March 21 in the Journal of Clinical Oncology.

Nevetheless, editorialists Max Wicha, MD, and Daniel Hayes, MD, from the University of Michigan Comprehensive Cancer Center in Ann Arbor, emphasize that "the clinical utility of monitoring CTC levels remains controversial," and although its potential is exciting, it remains "unproven."

Lack of Specificity

The assay for CTCs that has been most widely studied, and the only one approved for clinical use by the US Food and Drug Administration, is CellSearch (Veridex).

However, one of the problems with this assay, and other assays that have been available to date, is low sensitivity and poor specificity, say the editorialists. Some of the cells that are detected turn out, after careful scrutiny, not to be cancer cells after all; others are technically cancer cells but turn out to lack the ability to invade, proliferate, and metastasize.

"Not all detected cells are bad and not all bad cells are detected," the editorialists succinctly summarize.

New Assay From Japan

The new assay is described in a paper by Hisae Iinuma, PhD, and colleagues from the Teikyo University School of Medicine in Tokyo, Japan, that also appears in the March 21 in the Journal of Clinical Oncology. The assay uses multiple genetic markers to identify cancer cells, including cancer stem-like cells.

Dr. Iinuma and colleagues report a study of 735 patients with colorectal cancer, and conclude that the assay was useful in determining which patients were at high risk for recurrence and poor prognosis.

The editorialists point out several limitations to the study, and say that the results are "not ready yet for use when making clinical decisions."

But they are enthusiastic about the potential for this assay, which appears to home in on circulating tumor stem cells.

Dr. Wicha is a leading expert on cancer stem cells, and his lab was part of the team that first discovered such cells in breast cancer. His coeditorialist, Dr. Hayes, has published on tumor markers and on circulating tumor cells in breast cancer.

Stem Cells Drive Tumor Growth

Cancer stem cells are the cells that lie at the very heart of each tumor. They are the cancer cells with the "greatest invasive and metastatic capacity," the editorialists note, and they are thought to be responsible for micrometastasis.

Hence, the study by Dr. Iinuma and colleagues "raises fascinating hypotheses that could and should be addressed," they write.

This assay for measuring cancer stem cells in the bloodstream "could have enormous utility for directing adjuvant therapy for patients," they suggest.

"It could also have implications for future clinical trials of new therapeutic agents," they add.

Currently, responses to anticancer drugs are measured by assessing the impact the drug has on the whole tumor (such as by the degree of shrinkage).

However, it might be more important to assess the impact of the drug on the much rarer population of cancer stem cells that drive tumor growth and metastases. This has been done in a clinical trial in patients with breast cancer, but it requires tissue samples to be taken from the tumor before and after treatment. For patients with solid malignancies, this means undergoing multiple serial biopsies.

Measuring circulating tumor stem cells in the blood offers a way of assessing the impact of a therapy on the cancer stem cell population without requiring biopsies, the editorialists explain. In addition, such technologies would facilitate the development of therapies aimed at cancer stem cells, they add.

Dr. Iinuma and colleagues have disclosed no relevant financial relationships. Both editorialists report serving in an advisory or consultancy role for OncoMed Pharmaceuticals, Pfizer, and Dompe. Dr. Wicha reports owning stock in OncoMed, and receiving research funding from Dompe. Dr. Hayes reports receiving research funding from Veridex, Pfizer, and Novartis.

J Clin Oncol. Published online March 21, 2011. Abstract, Abstract

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