**Author details**

the wide-array targets would be more realistic. Similarly, drugs that would induce multiple cell death pathways are likely to circumvent cancer resistance to chemotherapy. Targeting drug transporter protein would be an effective approach to overcome cancer resistance to chemotherapy. Combined therapies are also considered to be a possible way to overcome cancer resistance to chemotherapy. An ongoing clinical study, led by Okonogi and his colleagues [32], applied maximum dose of carbon ion radiotherapy (C-ion RT) with concurrent chemotherapeutic drugs in uterine cervical carcinoma. The overall survival rate of 31 patients with recommended dose (RD) treatment is 88%; only 2 patients suffered from gastrointestinal toxicities. The studies still require developing a better drug delivery method for longer treatment duration and larger crowd of patients. Taking advantages of the advance in material science and nanotechnology, nanomedicine delivery systems show a promising potential to guarantee the efficacy of chemotherapy. For example, cerium oxide nanoparticles (CNPs) have been used as carriers to deliver curcumins [33]. The nanoscale delivery systems maintain the stability of curcumins in alkalescency environment and exert anticancer effects. The treatment with nanomedicines increases ROS accumulation and decreases the ratio of Bcl-2/Bax in human neuroblastoma cells, improving the therapeutic efficacy. Zhang et al. [34] used Dox-loaded DNA tetrahedron to target folate

receptors in HT-29 colon cancer cells. The treatment efficacy was also enhanced.

Apoptosis is an essential process for the growth and development of organisms, while cancer cells obtain immortality by escaping programed cell death. Understanding the underlying mechanism of cancer resistance to chemotherapy is fundamental for efficient cancer treatment agents. In this chapter, we have discussed the mechanisms of cancer cells evading apoptosis, including downregulation of pro-apoptotic signals, upregulation of anti-apoptotic signals and abnormal cross talk of autophagy and apoptosis. Chemotherapeutic drugs induce pro-apoptosis in cancer cells; however, the upregulation of anti-apoptotic proteins, e.g. Bcl-2 and IAPs, would cause cancer resistance. Death receptors including NF-κB-, PI3/AKT-, and p53-related signaling pathways are also involved in the chemoresistance. Additionally, the aberrant autophagy may cause apoptosis evasion as well through autophagic protein regulation, caspase activation, and autophagic degradation. A further, in-depth understanding of apoptosis evasion would be helpful for developing strategies to circumvent cancer resistant to chemotherapy. Combined chemotherapeutic treatment, drugs targeting multiple targets, and using nanoscale drug delivery (nanomedicine) show promising potentials to overcome

**4. Conclusions**

chemoresistance and achieve precision therapy.

132 Current Understanding of Apoptosis - Programmed Cell Death

AIF Apoptosis-inducing factor

Apaf-1 Apoptotic protease-activating factor

**Acronyms and abbreviations**

Lichan Chen, Yanyun Zeng and Shu-Feng Zhou\*

\*Address all correspondence to: szhou@hqu.edu.cn

Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, China
