**4.4. Ovarian cancer**

Epithelial ovarian cancer is the sixth most common cancer in women worldwide and it is still the most lethal gynecologic malignancy (Iorio*, et al.*, 2007)**.** Application of new technologies for detection of ovarian cancer could have an important effect on public health, but to achieve this goal, specific and sensitive molecular markers are essential (Petricoin*, et al.*, 2002)**.** Aldehyde dehydrogenase-1A1 (ALDH1A1) has been a valid marker among several malignant and non-malignant tissues in spite of several stem cell markers to identify CSCs. ALDH plays a role in the biology of TICs as well as being a stem cell marker. Because ALDH1A1 is implicated in chemo resistance pathways, it is questioned that targeting ALDH1A1 can effect cells resistant to chemotherapy and represent a potential target for cancer stem-cell-directed therapy. In a study, ALDH1A1 was investigated in ovarian cancer cell lines and patient samples and examined whether targeting ALDH1A1 sensitizes cells to

chemotherapy in both *in vitro* and *in vivo* ovarian cancer models. They showed that ALDH1A1 expression and activity have increased chemo resistant ovarian cancer cell lines. Most importantly, down-regulation of ALDH1A1 expression has sensitized normally chemo resistant tumors to both docetaxel and cisplatin *in vitro* and in mouse models. Besides being a stem cell marker, ALDH1A1 is also a viable target for therapy and a mediator of the aggressive phenotype (Landen*, et al.*, 2010).

Aldehyde Dehydrogenase: Cancer and Stem Cells 17

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).

the identification of non-neoplastic SCs and TSCs (Ginestier*, et al.*, 2007).

colorectal cancer (Huang*, et al.*, 2009) and GBM (Rasper*, et al.*, 2010).

ALDH1B1 may be a marker for colon cancer diagnosis.

**4.8. Colon cancer** 

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

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

Most colon cancers are adenocarcinomas that release mucus and other cellular secretions. In the United States in 2012, estimated new cases and deaths from colon and rectal cancer are reported as: 103,170 colon cancers and 51,690 deaths (Levin*, et al.*, 2008). Studies showed that ALDH1B1 and ALDH1A1 are differentially expressed in normal human tissues, but ALDH1B1 is expressed at higher levels than ALDH1A1 in human epithelial cancers. ALDH1B1 was abundantly expressed in adenocarcinomas originating from the tissue and particularly in colonic adenocarcinoma (Chen*, et al.*, 2011). Thus it can be deduced that
