**4.7. Brain cancer**

Glioblastoma (GBM) is the most common primary brain tumor in adults with an approximately 15-month survival (Stupp*, et al.*, 2005). Although there are several studies to improve the postoperative therapeutic applications within the last few years, there is not enough succes for this highly aggressive tumor. After resection, radiation, and chemotherapy regimens, relapses occur regularly. Thus, it is thought that this can be a clue to the presence of tumor stem cells (TSCs). This cellular subfraction within GBM causes continuous tumor growth and resistance to drugs and radiation (Rasper*, et al.*, 2010). TSCs are believed to nestle in the tumor, keeping it alive and growing, providing pluripotency, self-renewal, and resistance to chemo and radiation therapy(Reya*, et al.*, 2001). The first malignancies from which cells could be isolated and showed the potential to self-renew and to drive tumor formation and growth were leukemias (Bonnet & Dick, 1997). After that, a stem cell subfraction was described in brain tumors (Singh*, et al.*, 2003). This was the first study that identified and showed a population with stem cell properties in pediatric solid brain tumors. Those cells were identified by their ability to proliferate under serum-free cell culture conditions and by the expression of CD133 and nestin. CD133 has long remained the most important TSC marker in malignant glioma. On the other hand, ALDH1 is a cytoplasmatic stem cell marker in a variety of malignant tumors and catalyzes the oxidation of intracellular aldehydes including the transformation of retinol to RA. As mentioned above, RA is a modulator of cell proliferation and differentiation that possibly contributes to the maintenance of an undifferentiated stem cell phenotype. Jones et al. presented a method to isolate human cells via flow cytometry depending on the amount of cytosolic ALDH (Jones*, et al.*, 1995). Recently, Ginestier et al. found ALDH1 to be a stem cell marker in breast carcinoma associated with poor clinical outcomes (Ginestier*, et al.*, 2007). Since then, ALDH1 has been described as a marker of stemness in other solid malignancies including lung cancer (Jiang*, et al.*, 2009) and colorectal cancer (Huang*, et al.*, 2009).

Therefore, identification and isolation of these cells seem crucial for a better understanding of tumor behavior, origin, and therapy. Recently, ALDH1 has been described as a marker for the identification of non-neoplastic SCs and TSCs (Ginestier*, et al.*, 2007).

So far, cellular markers including CD133 have been used to identify TSCs in GBMs, but recently, CD133-negative GBMs are characterized to behave as brain TSCs (Beier*, et al.*, 2007).

Therefore, ALDH1 has also been described as a stem cell marker in various solid neoplasms including lung cancer (Jiang*, et al.*, 2009), breast carcinoma (Ginestier*, et al.*, 2007), and colorectal cancer (Huang*, et al.*, 2009) and GBM (Rasper*, et al.*, 2010).
