Circulating tumor cells (CTCs) are cancer cells that detach from a primary cancer tumor and enter a person’s bloodstream. Their goal is to move to another part of the body to form new metastases. These new metastatic lesions are more aggressive than the primary tumor and account for most of the cancer-related deaths.

Recently, we have become aware that CTCs play a significant role in the process of developing these new lesions. To form metastatic tumors, CTCs must pass through specific steps that are crucial for the metastatic process.

First, CTCs must detach from the primary lesion and intravasate (get) into the bloodstream or the lymphatic vessels. Once into the circulation, these CTCs move through the body and propagate along with numerous other blood cells unless they reach a target tissue. The second step is for the CTCs to extravasate into micro-vessels of the target tissue, adapt to their new microenvironment, and then reproduce and colonize to form new, distant metastases.

Successful formation of the metastatic growth primarily depends on the ability of CTCs to evade the host’s immune system, adapt to new environment, survive, increase, and then trigger neoangiogenesis (formation of new blood vessels in tumors).

Importance of CTCs in Cancer Care

CTCs are considered as a potential biomarker for evaluating prognosis in patients with metastatic lesions as well as potential therapeutic targets for controlling or preventing tumor metastasis. CTCs can be used to assess the response of cancer patients to a particular therapy, categorizing high-risk and low-risk patients by detecting CTCs in early-stage cancers, identifying patients based on the need for surgery or chemotherapy, and monitor the recurrence of the tumor.

Analysis of the molecular properties of CTCs can provide significant insight into the genotypic and phenotypic characteristics of a tumor without the need to perform an invasive biopsy. Besides, since detection of CTC does not require any invasive method, it is relatively easy to frequently monitor tumor progression and check incidences of drug-resistance through both counting and molecular profiling of CTCs.

CTC as a Prognostic Biomarker

In recent years, many studies have been performed to detect the numbers of CTCs in blood to evaluate cancer prognosis and outcomes. It has been found in one of such studies that breast cancer patients with CTCs ≥ 5 have shorter median progression-free and overall survival compared to patients with CTCs less than 5.

A similar scenario has also been observed in patients with metastatic prostate cancer. In the case of colorectal cancer patients, CTC number ≥ 3 is found to be associated with significantly worse median progression-free and overall survival compared to CTC number less than 3.

Understanding the role of CTCs and how to utilize this information is essential today. Its importance for good cancer care will continue to expand as our understanding of the role CTCs play in moving lethal cancer ahead.

• http://www.annclinlabsci.org/content/43/3/295.full

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126032/

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453029/

• http://science.sciencemag.org/content/341/6151/1186

Joel T Nowak, MA, MSW