Motivation

Tumor mobility is likely the most significant prognostic factor for all types of cancer. Contained primary tumors often present no symptoms and if discovered early can be safely removed without needing subsequent chemotherapy. If left untreated, however, primary tumors spread through the lymphatic or blood circulatory systems to other parts of the body. Given enough time, the cancer cells transition and take on the forms of cells from other organs. At this stage, the cells invade compatible organs and secondary tumors called Mets develop. Early mets are less diverse and still present hope for treatment. Later mets, however, are too diverse and are usually associated with terminal diagnosis.

The difference between early stage and late stage diagnosis can be staggering. The table below lists the survival rate differential between early and late diagnosis for common cancer types.

Early detection of cancer and its localization is very difficult. General early detection tests look for specific molecular traces in samples of blood or urine. Such tests usually carry a high rate of false positives and are difficult to calibrate for each individual. In addition, these test provide limited information regarding the primary and secondary tumor sites. Indeed, the localization of tumors is a real issue. Total body scans are impractical at the necessary resolution level and carcinogenic if applied regularly.

Circulating tumor cells (CTCs) provide an alternate path for tumor detection. These stray cells originate from the tumor site and enter the blood stream after begin pushed out from the forefront of the primary tumor. These stray cells are also the first to invade other organs and seed secondary tumors. During the process of detachment and invasion CTCs undergo several transitions downregulating local adhesian molecules and upregulating distal adhesian molecules and stem cell markers. Deciphering CTC surface markers holds the key to understanding the tumor's ability to invade the host system.

Methods and tools for detecting circulating tumor cells (CTCs) are very limited. CELLSEARCH circulating tumor cell test is the only FDA approved diagnostic method. CTCs are magnetically separated from samples of peripheral blood using the common epithelial marker EpCAM.Subsequently, the cells are stained and individually scanned using an automated positioning and scanning system. Final results are submitted to an expert for review. In clinical practice, however, simple enumeration of CTCs is most commonly used. Another diagnostic waiting for FDA approval is Adnatest, which goes a step further with broad spectrum separation of cells and RT PCR analysis. Multiple antibodies are used to capture not only EpCAM+ cells but also CA15-3+, Her2new+ and others. RT PCR kits are targeted at common primary tumors. Customised CTC screens are possible for research purposes only through immunostaining in combination with microdisection.

The takeaway message is current CTC diagnostic tests are time consuming, require advanced training and equipment, are impractical for early diagnosis, and are too broad to yield localization or mobility information.