Recently, antiviral RNA interference (RNAi) usingshort-interfering RNA (siRNA) has been developed asa novel strategy and tested in clinical trials. siRNAshave been demonstrated to selectively silence not onlyendogenous genes in mammalian cells (Sui et al.,2002; Yu et al., 2002) but also viral genes in virus-induced diseases (Kitabwalla and Ruprecht, 2002; Geet al., 2003; Milner, 2003). Several RNAi studies wereperformed with human tumor cell lines using syn-thetic siRNAs or short hairpin RNAs (shRNAs) li-braries to identify the modulators of anticancer drugsensitivity (Bartz et al., 2006; Ji et al., 2007; Swantonet al., 2007; Whitehurst et al., 2007; Honma et al.,2008; Bauer et al., 2010). Combination therapy withsiRNA may significantly enhance the sensitivity ofcancer cells to the anticancer therapy and thereby helpprevent the development of Chemo/Radio resistanceresulting from low-dose Chemo/Radio therapy (Fig. 1).Previously, the approach using synthesized siRNApools was employed to identify the chemosensitizer inNCI-H1155, a human non-small-cell lung cancer line(Whitehurst et al., 2007). A set of 87 candidate pacli-taxel-sensitizing genes, including receptor–ligand pairs,proteasome, microtubules, testis antigens, and Rasfamily, were identified. In addition, a major contribu-tion of mitotic progression-related genes in cancercells was also highlighted. Other study performed byJung validated the role of 2-in-1 antiviral siRNAtargeting human papillomavirus (HPV)