**3. Head and neck cancer**

Head and neck squamous cell carcinoma (HNSCC) is the most popular head and neck cancer and is the sixth most common cancer in the world. They include malignancies originated from the epithelia of larynx, pharynx, oral and nasal cavities.

Application of Host Cell Reactivation in Evaluating the Effects of Anticancer Drugs

progression (Vora et al., 2003).

**3.3 Treatment of HNSCC** 

exposure and survival of these patients (Marsit et al., 2004).

and side effects for efficient treatment of HNSCC is still under looking for.

**an effective therapeutic strategy for this malignancy** 

and Environmental Toxicants on Cellular DNA Repair Activity in Head and Neck Cancer 469

Previous investigations showed that LOH of chromosome 17q (*BRCA1* locus) were found in 35% to 56% of laryngeal cancer (Kiaris et al., 1995; Rizos et al., 1998). In contrast, studies using CGH found an overrepresentation of 17q in 9% to 47% of HNSCC (Bockmuhl et al., 1996; Brieger et al., 2003), and one array-CGH reported the gain of 17q21 in 33% (7/21) of oral cancer (Sparano et al., 2006). These controversial results by genome-wide analyses may be due to the physically close localization of *ERBB2* (HER-2/neu) oncogene and the results need to be clarified by specifically looking at the *BRCA1* gene locus. Regarding the expression of *BRCA1* in HNSCC, one study showed that BRCA1 immunostaining positivity was lost in 34% (26/77) of tongue cancers, which might be correlated with early-stage tumor

The results of genome-wide studies also suggest that genetic alterations at *RAD51* (15q15.1) and *XPC* (3p25) loci may be present in HNSCC (Bockmuhl et al., 1996; Brieger et al., 2003; Partridge et al., 1999; Sparano et al., 2006; van den Broek et al., 2007). Altered RAD51 protein expression has been reported by one pilot study with twelve head and neck cancer patients (Connell et al., 2006). The patients with high RAD51 protein levels in their pre-treatment tumor biopsies demonstrate poorer cancer-specific survival rates than those with lower RAD51 levels (33.3% vs. 88.9% at 2 years; *P* = 0.025). These results suggest that RAD51 expression may influence the outcome of with head and neck cancer patients who receive chemotherapy and radiotherapy (Connell et al., 2006). Other reports regarding altered expression of DNA repair genes in HNSCC include Ku80 (Chang et al., 2006), NBN and ERCC1 (Hsu et al., 2010; Yang et al., 2006). It has been shown that ERCC1 expression is associated with cisplatin resistance (Handra-Luca et al., 2007; Hsu et al., 2010) and NBN is correlated with outcome of advanced HNSCC patients (Yang et al., 2006). Inactivation of the BRCA/FA pathway via promoter methylation has also been described in HNSCC, and may be related to tobacco and alcohol

Since HNSCC and its treatment can affect important physiological functions, such as speaking, breathing, and swallowing, it is important for choosing the appropriate treatment that not only cures but also benefits to the preservation of organs, physiological functions, and quality of life. The standard treatment for resectable HNSCC is surgical resection with or without postoperative concurrent chemotherapy (cisplatin plus 5-fluorouracil) and radiotherapy (CCRT). Around two-thirds of HNSCC are in advanced stage at time of diagnosis (Specenier & Vermorken, 2009). The majority of these patients with advanced stage tumors finally relapse locoregionally or at distant sites. These patients are usually qualified for palliative treatment only. Recent advances in using cetuximab (anti-EGFR) to prolong patient's survival time in locally advanced HNSCC is a big, but still not a fully satisfied progress (Vermorken et al., 2008). The use of docetaxel (a spindle poison and mitotic catastrophe inducer) can enhance the efficacy of chemotherapy using cisplatin/fluorouracil and improve slightly the overall survival rates of HNSCC patients (Hitt et al., 2005; Posner et al., 2007; Vermorken et al., 2007). These results suggest that a combination regimen exploiting different cell-killing mechanisms may be superior to monotherapy. However, an ideal combination regimen with lower adverse

**3.4 Understanding the status of DNA repair genes in HNSCC is important for design of** 

Since DNA repair genes/activity play a key role in cancer development and treatment, understanding their expression and genomic/functional alterations may facilitate the
