54
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Broad targeting of resistance to apoptosis in cancer

      research-article

      a , b , , a , c , d , e , f , g , h , i , a , j , k , l , m , m , n , n , o , p , q , q , r , s , s , t , u , v , w , w , x , y , y , z , z , aa , ab , ac , ac , ad , ae , a

      Seminars in cancer biology

      Apoptosis, Necrosis, Autophagy, Apoptosis evasion, Nuclear transporters, natural, chemopreventive agents

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.

          Related collections

          Most cited references 434

          • Record: found
          • Abstract: found
          • Article: not found

          The role of autophagy in cancer development and response to therapy.

          Autophagy is a process in which subcellular membranes undergo dynamic morphological changes that lead to the degradation of cellular proteins and cytoplasmic organelles. This process is an important cellular response to stress or starvation. Many studies have shed light on the importance of autophagy in cancer, but it is still unclear whether autophagy suppresses tumorigenesis or provides cancer cells with a rescue mechanism under unfavourable conditions. What is the present state of our knowledge about the role of autophagy in cancer development, and in response to therapy? And how can the autophagic process be manipulated to improve anticancer therapeutics?
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Missing pieces in the NF-kappaB puzzle.

            The regulation of the transcription factor NF-kappaB activity occurs at several levels including controlled cytoplasmic-nuclear shuttling and modulation of its transcriptional activity. A critical component in NF-kappaB regulation is the IkappaB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-kappaB and IKK.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function.

              Apoptosis is initiated when Bcl-2 and its prosurvival relatives are engaged by proapoptotic BH3-only proteins via interaction of its BH3 domain with a groove on the Bcl-2-like proteins. These interactions have been considered promiscuous, but our analysis of the affinity of eight BH3 peptides for five Bcl-2-like proteins has revealed that the interactions vary over 10,000-fold in affinity, and accordingly, only certain protein pairs associate inside cells. Bim and Puma potently engaged all the prosurvival proteins comparably. Bad, however, bound tightly to Bcl-2, Bcl-xL, and Bcl-w but only weakly to A1 and not to Mcl-1. Strikingly, Noxa bound only Mcl-1 and A1. In accord with their complementary binding, Bad and Noxa cooperated to induce potent killing. The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets.
                Bookmark

                Author and article information

                Journal
                9010218
                1211
                Semin Cancer Biol
                Semin. Cancer Biol.
                Seminars in cancer biology
                1044-579X
                1096-3650
                30 December 2015
                28 April 2015
                December 2015
                01 December 2016
                : 35
                : 0
                : S78-S103
                Affiliations
                [a ] Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
                [b ] Interim translational Research Institute, Hamad Medical Corporation, Doha, Qatar
                [c ] Getting to Know Cancer, Truro, Nova Scotia, Canada
                [d ] C-SET, [Jackson, #229] State University, Jackson, MS, United States
                [e ] Department of Life Sciences, Tzu-Chi University, Hualien, Taiwan
                [f ] Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
                [g ] Department of Pathology and Cell Biology, Columbia University, New York City, NY, United States
                [h ] Dipartimento di Scienze per la Qualità della Vita Alma Mater Studiorum-Università di Bologna, Italy
                [i ] Moffit Cancer Center, University of South Florida College of Medicine, Tampa, FL, United States
                [j ] Departments of Pharmacology and Pathology, Karmanos Cancer Institute, Detroit MI, United States
                [k ] The School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China
                [l ] Sanus Bioscience, San Diego, CA, USA
                [m ] Institute of Food Sciences National Research Council, Avellino, Italy
                [n ] Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, United States
                [o ] Mor-NuCo, Inc, Purdue Research Park, West Lafayette, IN, United States
                [p ] Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom
                [q ] Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan
                [r ] Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Zografou 15780, Athens, Greece
                [s ] Department of Experimental and Clinical Medicine, university of florence, Italy
                [t ] Department of Biology, College of Science, UAE University, United Arab Emirates
                [u ] Faculty of Science, Cairo University, Egypt
                [v ] Department of Chemistry, College of Science, UAE University, United Arab Emirates
                [w ] Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, United States
                [x ] Department of BioMedical Sciences, School of Medicine Creighton University, Omaha NE, United States
                [y ] School of Chemical and Bio Technology, SASTRA University, Thanjavur, India
                [z ] Department of Biology, University of Rome “Tor Vergata”, Italy
                [aa ] Ovarian and Prostate Cancer Research Trust Laboratory, Guildford, Surrey, United Kingdom
                [ab ] Department of Comparative Pathobiology and Purdue University Center for Cancer Research, Purdue, West Lafayette, IN, United States
                [ac ] Institute of Cancer Sciences, University of Glasgow, Glasgow, Ireland
                [ad ] Department of Pathology, New York Medical College, Valhalla, NY, United States
                [ae ] Mayo Graduate School, Mayo Medical School, Mayo Clinic Medical Scientist Training Program, Rochester, MN, United States
                Author notes
                [] Corresponding author at: Department of Oncology, Wayne State University, Karmanos Cancer Institute, 732 HWCRC Building, Detroit, MI 48201, United States. Tel.: +1 313 576 8329; fax: +1 313 576 8389. mohammar@ 123456karmanos.org (R.M. Mohammad).
                Article
                NIHMS747941
                10.1016/j.semcancer.2015.03.001
                4720504
                25936818

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                Categories
                Article

                Comments

                Comment on this article