**3. Summary**

In this chapter, we show that arsenical compounds enhance cancer cell apoptosis when combined with other anticancer therapeutics including radiation, chemotherapies, and moleculartargeted drugs. Although a number of reports have shown the anticancer effects of arsenic and have discussed the possible molecular targets of ATO in malignant cells, molecular mechanisms underlying ATO-based synergistic anticancer effects with other anticancer therapeutics remain obscure. In the past decade, next-generation sequencing (NGS) technologies have tremendously improved and have clarified the whole context of genomic alterations in cancer cells, among which phenotypic and functional heterogeneity arises within the same tumor as a consequence of genetic changes, environmental differences, and anticancer therapy [121–123]. This indicates that the possibility of targeting single molecules and/or signaling pathways as well as single cellular biological processes may generate a different malignant population of cancer cells, some of which may acquire a certain drug resistance. Therefore, novel therapeutic agents and/or strategies are required to overcome drug resistance and improve both the disease outcome and the quality of life for patients with cancer. Further understanding of the relationship between induction of apoptosis and genetic/epigenetic changes in cancer cells may contribute to improvement in selectivity for cancer treatment. Additional studies are required to understand the synergistic anticancer action regarding ATO-based combination therapeutics to develop a novel combined therapy for cancer.
