**3. Possible approaches to overcoming cancer resistance**

In clinical treatments, the principle to treat drug-resistant cancer is targeting the specific target with the coordinated agent. However, the strategy is idealized since drug-resistant cancer usually involves multiple signaling pathways as well as multiple targets, and the contributions of each target is hard to be calculated. Therefore, treating drug-resistant cancer with the drugs against 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.

ATG9 Autophagy protein 9

FoxO Forkhead-box class O

MDR Multidrug resistance

NSCLC Non-small cell lung cancer

DOX Doxorubicin

GA Gambogic acid

P-gp P-glycoprotein

**Author details**

**References**

Lyon, France; 2013

Clinicians. 2015;**65**:5-29

TOP-1 Topoisomerase-1

TNF Tumor necrosis factor

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

Huaqiao University, Xiamen, Fujian, China

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

DISC Death-inducing signaling complex

IAP Inhibitors of apoptosis protein

MDM2 Mouse double minute 2 homolog

BH3-only protein Bcl-2 homology domain only protein

MAC Mitochondrial apoptosis-induced channel UVRAG UV radiation resistance-associated gene

MOMP Mitochondria outer membrane permeabilization

DRAM Downregulated damage-regulated autophagy modulator

Role of Apoptosis in Cancer Resistance to Chemotherapy

http://dx.doi.org/10.5772/intechopen.80056

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Department of Bioengineering and Biotechnology, College of Chemical Engineering,

[1] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARCCancerBase No. 11 [Internet].

[2] Siegel RL, Miller KD, Jemal DVM A. Cancer statistics, 2015. CA: A Cancer Journal for

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.
