Kumar et al., Med chem 2015, 5:3 DOI: 10.4172/2161-0444.1000252 Review Article Open Access Med chem ISSN: 2161-0444 Med chem, an open access journal Volume 5(3): 115-123 (2015) - 115 Drug Targets for Cancer Treatment: An Overview Shashank Kumar 1 , Mohammad Kaleem Ahmad 1 , Mohammad Waseem 1 and Abhay K Pandey 2 * 1 Molecular and Cell Biology Laboratory, Department of Biochemistry, King Georges Medical university, Lucknow-226003, India 2 Department of Biochemistry, University of Allahabad, Allahabad-211002, India *Corresponding author: Abhay K. Pandey, Department of Biochemistry, University of Allahabad, Allahabad-211002, India, E-mail: akpandey23@rediffmail.com Received February 24, 2015; Accepted March 17, 2015; Published March 19 2015 Citation: Kumar S, Ahmad MK, Waseem M, Pandey AK (2015) Drug Targets for Cancer Treatment: An Overview. Med chem 5: 115-123. doi:10.4172/2161- 0444.1000252 Copyright: © 2015 Kumar S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Cancer is one of the major cause of death worldwide. Malignant cells display metabolic changes, when compared to normal cells, because of both genetic and epigenetic alterations. Number of drugs being used for the cancer treatment follows different mechanisms of action. Therapeutic strategies include targeting of drugs at specifc genes or proteins/enzymes found in cancer cells or the internal tissue environment which contributes to growth and survival of these cells. Targeted therapy is often used along with chemotherapy and other treatments to restrict the growth and spread of cancer cells. During the past few decades, targeted therapy has emerged as a promising approach for the development of selective anticancer agents. There is a class of targeted therapy drugs called angiogenesis inhibitors which focus on blocking the development of new blood vessels in tumor tissues. In addition, anticancer drugs also include DNA intercalators, DNA synthesis inhibitors, transcription regulators, enzyme inhibitors etc. This review focuses on major classes of anticancer drug targets and their therapeutic importance. Keywords: Anticancer drug targets; Angiogenesis; Gene regulation; Enzyme; Microtubules Introduction Cancer is the second leading cause of death in Europe and America. Tremendous resources are being invested all around the world for developing preventive, diagnostic, and therapeutic strategies for cancer [1]. Several pharmaceutical companies and government/ non-government organizations are involved in the discovery and development of anticancer agents [2]. Identifcation of novel cytotoxic compounds has led to the development of anticancer therapeutics for several decades. Boom of knowledge in molecular sciences, genomics and proteomics has also helped in creating new potential drug targets. Tis has changed the paradigms of anticancer drug discovery toward molecularly targeted therapeutics. Tere are unique challenges and opportunities in discovery of anticancer drug delivery which might refect at each stage of the drug development process [3]. Cancer is primarily a disease of uncontrolled cell division, thus identifcation of anti-proliferative compounds and their efects on regression of tumor size are the main aims for therapeutic discovery. For this purpose murine models of cancer were developed and several clinically important anticancer compounds were identifed [1]. Diferentiated result outputs among fast growing and slow growing tumors led investigators to modify the screening protocols to include a variety of cell lines and tumor types. Te rationale that cancer cells are more likely to be replicating than normal cells makes the basis for targeting cell division process by most of the chemotherapeutics. Unfortunately signifcant toxicity is associated with chemotherapeutics as they lack specifc action [1-3]. Double-helical DNA consists of two complementary strands running anti-parallel having sugar-phosphate poly- deoxyribonucleotide backbone associated with specifc hydrogen bonding between nucleotide bases [4]. In a given DNA sequence diference in chemical feature of the molecular surfaces in either groove forms the basis for molecular recognition by small molecules and proteins. B-form of the DNA i.e. biologically relevant double helix is characterized by a shallow wide major groove and a deep narrow minor groove [5]. DNA replication, transcription and protein synthesis are the major steps in cell growth and division. Being carrier of genetic information as well as central to tumorigenesis and pathogenesis, DNA is a major target for drug development. Tere is always a challenge for drug to achieve maximum specifc DNA binding afnity. Te other thing that needs consideration is that drug should not afect cellular and nuclear transport activity of the normal cells. Some of the most efective anticancer agents that target DNA are known to produce signifcant survival rate in cancer patients when used in combination with drugs having diferent mechanisms of action [6]. Besides DNA, RNA, enzymes and other proteins also contributes as major targets for anticancer drug development [7]. Structures of some anticancer drugs are depicted in Figure 1. In this review we have tried to discuss some molecular aspects of anticancer drug mechanisms. Angiogenesis Inhibitors Angiogenesis (AG) is the process by which tumour develops new blood supply (neovascularisation) for the growth and metastasis. Small tumours can obtain oxygen and nutrients by difusion but as they become enlarged they need to develop new blood vessels for the fulfllment of required nutrients for growth, invasion and metastasis. Diferent anti- and pro-angiogenic factors are involved in the development of blood vessels in a complex equilibrium [8]. In physiological processes such as wound healing this equilibrium may go in favor of angiogenesis by infammation or hypoxia. But on the other hand it may be the part of the pathological process in cancer or other chronic infammatory diseases. Vascular endothelial growth factor (VEGF), angiogenin, transforming growth factor-β (TGF-β) and fbroblast growth factor (FGF) are some pro-angiogenic factors that are released in tumor associated angiogenesis which in turn induces the proliferation, migration and invasion of endothelial cells in new vascular structures [8]. Platelet derived growth factor receptor and cell adhesion molecules (e.g., integrins) play important role in the process of angiogenesis. Oxygen deprivation, oncogenic mutations, infammation and mechanical stress are the stimulus that initiates growth of new vessels in tumor (angiogenic switch). Tis leads to vascularisation M e d i c i n a l c h e m i s t r y ISSN: 2161-0444 Medicinal chemistry