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      Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics

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          Abstract

          Various physiological processes involve appropriate tissue developmental process and homeostasis - the pathogenesis of several diseases connected with deregulatory apoptosis process. Apoptosis plays a crucial role in maintaining a balance between cell death and division, evasion of apoptosis results in the uncontrolled multiplication of cells leading to different diseases such as cancer. Currently, the development of apoptosis targeting anticancer drugs has gained much interest since cell death induced by apoptosis causes minimal inflammation. The understanding of complexities of apoptosis mechanism and how apoptosis is evolved by tumor cells to oppose cell death has focused research into the new strategies designed to induce apoptosis in cancer cells. This review focused on the underlying mechanism of apoptosis and the dysregulation of apoptosis modulators involved in the extrinsic and intrinsic apoptotic pathway, which include death receptors (DRs) proteins, cellular FLICE inhibitory proteins (c-FLIP), anti-apoptotic Bcl-2 proteins, inhibitors of apoptosis proteins (IAPs), tumor suppressor (p53) in cancer cells along with various current clinical approaches aimed to selectively induce apoptosis in cancer cells.

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          Most cited references126

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          Knocking down barriers: advances in siRNA delivery

          Key Points RNA interference (RNAi) is a fundamental pathway in eukaryotic cells by which sequence-specific small interfering RNA (siRNA) is able to silence genes through the destruction of complementary mRNA. RNAi is an important therapeutic tool that can be used to silence aberrant endogenous genes or to knockdown genes essential to the proliferation of infectious organisms. Delivery remains the central challenge to the therapeutic application of RNAi technology. Before siRNA can take effect in the cytoplasm of a target cell, it must be transported through the body to the target site without undergoing clearance or degradation. Currently, the most effective synthetic, non-viral delivery agents of siRNA are lipids, lipid-like materials and polymers. Various cationic agents including stable nucleic acid–lipid particles, lipidoids, cyclodextrin polymers and polyethyleneimine polymers have been used to achieve the successful systemic delivery of siRNA in mammals without inducing significant toxicity. Direct conjugation of delivery agents to siRNA can facilitate delivery. For example, cholesterol-modified siRNA enables targeting to the liver. RNAi therapeutics have progressed to the clinic, where studies are being conducted to determine siRNA efficacy in treating several diseases, including age-related macular degeneration and respiratory syncytial virus. Moving forward, it will be important to pay close attention to the potential nonspecific immunostimulatory effects of siRNA. Modifications to siRNA can be used to minimize stimulation of the immune system, and an increased emphasis must be placed on performing proper controls to ensure that therapeutic effects are sequence-specific.
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            Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis.

            Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro-survival or pro-death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti-cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis-related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment. © 2012 Blackwell Publishing Ltd.
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              Revisiting the hallmarks of cancer.

              The hallmarks of cancer described by Hanahan and Weinberg have proved seminal in our understanding of cancer's common traits and in rational drug design. Not free of critique and with understanding of different aspects of tumorigenesis coming into clearer focus in the recent years, we attempt to draw a more organized and updated picture of the cancer hallmarks. We define seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.
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                Author and article information

                Journal
                Adv Pharm Bull
                Adv Pharm Bull
                Adv Pharm Bull
                APB
                TBZMED
                Advanced Pharmaceutical Bulletin
                Tabriz University of Medical Sciences
                2228-5881
                2251-7308
                June 2019
                01 June 2019
                : 9
                : 2
                : 205-218
                Affiliations
                Institute of Marine Biotechnology, Universiti Terengganu Malaysia, 21030 Terengganu, Malaysia.
                Author notes
                [* ] Corresponding Author: Gul-e-Saba Chaudhry, Tel: +609-6683810, Fax: +609-6683810, Email: gul.saba@ 123456umt.edu.my
                [# ]Both authors contributed as co-first authors.
                Author information
                https://orcid.org/0000-0001-9217-9084
                https://orcid.org/0000-0002-4555-8572
                Article
                10.15171/apb.2019.024
                6664112
                31380246
                f898713c-336a-48bd-93c2-39caf57fede7
                © 2019 The Author (s).

                This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers.

                History
                : 22 August 2018
                : 16 December 2018
                : 20 December 2018
                Page count
                Figures: 5, References: 173, Pages: 14
                Categories
                Review Article

                apoptosis,apoptosis pathways,cancer,c-flip,caspases,death receptors,targeted drugs

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