This field is currently in evolution. Efforts have been made to identify surface marker “signatures “ that are specific for each type of cancer (Table ​(Table2)2) It is worth noting that isolation of cancer cells is far from perfect and remains an area of controversy. Not all CSC express SC markers and some tumor cells that are not SC may also express those markers[1]. Great progress

has been already kinase inhibitors made in this area but this more works remains to be done. Table 1 Markers used in gastrointestinal cancer stem cell identification Table 2 Surface markers of gastrointestinal cancer stem cell Resistance of CSCs to anticancer therapy Several studies demonstrated that CSC exhibit resistance to chemotherapy agent[2,58]. One of the widely accepted theories is that the elevated levels of ATP-binding cassette (ABC) transporters mediate resistance to chemotherapy[2,3,58,59]. ATP transporters are membrane transporters that can pump small molecules including cytotoxic drugs out of cells in exchange for ATP hydrolysis[59]. CSC as well as normal SC appear to express high levels of ABC transporters[60]. This characteristic can lead to multidrug resistance and enhanced tumorigenesis. Evolving evidence suggests that numerous cell lines and tumors contain CSC, referred to as side population (SP) cells that possess a differentially greater capacity

to resist chemotherapeutic agents and invade surrounding tissues[2,61-63]. This phenomenon, however, may allow for development of therapies that could target ATP transporters in CSC. Targeting CSCs Targeting CSC is an intriguing concept that may offer several therapeutic advantages. Targeting

the inherently resistant CSC may overcome resistant to chemotherapeutic agents. Most patients with metastatic gastrointestinal cancers tend to experience treatment failure and resistance to palliative chemotherapy[64-66]. Additionally, targeting CSC may, not only improve efficacy of treatment but may also reduce therapy-related toxicity through developing treatment that are selective for CSC and not toxic to healthy tissues. Novel treatment strategies are, therefore, being developed that target surface markers on CSC, ATP-binding cassettes, key signaling pathways or their tumor microenvironment[1]. Targeting surface GSK-3 markers: Since CD133+ is expressed in CSC in gastrointestinal cancer, it represents an interesting target to selectively inhibit CSC. A recent study demonstrated that carbon nanotubes conjugated with CD133+ monoclonal antibodies caused photothermolysis of CD133+ glioblastoma cells when affixed to an anti-CD133 antibody that selectively targeted those cells[67]. This study represents an encouraging proof of concept that gastrointestinal CSC can be possibly targeted with similar strategies. Targeting cancer stem cell pathways: Targeting signaling pathways that are thought to be active in CSC is an ongoing area of active research.