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World J Transl Med. Dec 12, 2015; 4(3): 69-77
Published online Dec 12, 2015. doi: 10.5528/wjtm.v4.i3.69
Targeting apoptosis is the major battle field for killing cancers
Xiao-Chun Liu, Jiang-Ming Gao, Shan Liu, Li Liu, Jing-Rui Wang, Xian-Jun Qu, Bing Cai, Shu-Lin Wang
Xiao-Chun Liu, Jiang-Ming Gao, Shan Liu, Li Liu, Jing-Rui Wang, Bing Cai, Shu-Lin Wang, the Marine Biomedical Research Institute of Qingdao, Department of Pharmacology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266071, Shandong Province, China
Xian-Jun Qu, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100000, China
Author contributions: All the authors equally contributed to this work.
Supported by A grant from National Key Sci-Tech Special Project of Ministry of Science and Technology of China, No. 2008ZX10002-020; and grants from the National Natural Science Foundation of China, Nos. 30973390 and 81272249 (S. W).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest in this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shu-Lin Wang, MD, PhD, Professor, the Marine Biomedical Research Institute of Qingdao, Department of Pharmacology, School of Medicine and Pharmacy, Ocean University of China, 23 Hongkong East Rd. Marine Biomedical Research Building, Qingdao 266071, Shandong Province, China. shulinwang@ouc.edu.cn
Telephone: +86-532-80932613
Received: January 28, 2015
Peer-review started: January 28, 2015
First decision: April 10, 2015
Revised: April 27, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: December 12, 2015
Processing time: 321 Days and 19.4 Hours
Abstract

Targeting apoptosis is one of the major strategies for cancer therapy. Essentially, most of the conventional cancer therapeutic drugs that are in the clinical use induce apoptosis and in part necrosis of malignant cells and therefore prevent cancer progression and metastasis. Although these cytotoxic anticancer drugs are important weapons for killing cancers, their toxic side effects limited their application. The molecularly targeted therapeutics that are based on the deeper understanding of the defects in the apoptotic signaling in cancers are emerging and have shown promising anticancer activity in selectively killing cancers but not normal cells. The examples of molecular targets that are under exploration for cancer therapy include the cell surface receptors such as TNFR family death receptors, the intrinsic Bcl-2 family members and some other intracellular molecules like p53, MDM2, IAP, and Smac. The advance in the high-throughput bio-technologies has greatly accelerated the progress of cancer drug discovery.

Keywords: Apoptosis; Chemotherapy; Drug targets; Drug resistance; Cancer; Translational medicine

Core tip: Chemotherapy and radiotherapy are important approaches for cancer therapy and have prolonged the lifespan and reduced the mortality of cancer patients. But chemotherapy and radiotherapy induce apoptosis in both cancer and normal cells, therefore possessing severe toxic side effects. It appears quite important to develop the biological mechanism-based drugs that that can selectively kill tumor cells but not normal cells. Molecular targets in the apoptotic signaling pathways such as p53, TRAIL, and Bcl-2 have been identified, and molecularly targeting drugs for a variety of tumors based on these pathways are currently under development. Dissecting the genetic alterations in a particular tumor type and designing the rational drug combinations targeting different pathways can help achieve synergy in eradicating cancer cells and reversing drug resistance, and this holds great promise for the personalized treatment of cancer patients.