@article{e63b2f407f974d26a9abb1bd788703ed,
title = "Broad targeting of resistance to apoptosis in cancer",
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.",
keywords = "Apoptosis, Apoptosis evasion, Autophagy, Necrosis, Nuclear transporters, natural chemopreventive agents",
author = "Mohammad, {Ramzi M.} and Irfana Muqbil and Leroy Lowe and Clement Yedjou and Hsu, {Hsue Yin} and Lin, {Liang Tzung} and Siegelin, {Markus David} and Carmela Fimognari and Kumar, {Nagi B.} and Dou, {Q. Ping} and Huanjie Yang and Samadi, {Abbas K.} and Russo, {Gian Luigi} and Carmela Spagnuolo and Ray, {Swapan K.} and Mrinmay Chakrabarti and Morre, {James D.} and Coley, {Helen M.} and Kanya Honoki and Hiromasa Fujii and Georgakilas, {Alexandros G.} and Amedeo Amedei and Elena Niccolai and Amr Amin and Ashraf, {S. Salman} and Helferich, {William G.} and Xujuan Yang and Boosani, {Chandra S.} and Gunjan Guha and Dipita Bhakta and Ciriolo, {Maria Rosa} and Katia Aquilano and Sophie Chen and Mohammed, {Sulma I.} and Keith, {W. Nicol} and Alan Bilsland and Dorota Halicka and Somaira Nowsheen and Azmi, {Asfar S.}",
note = "Funding Information: NIH Grants R21 1R21CA16984801 and 1R21CA17597401 to RMM is acknowledged. This work was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars and State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011 to HJ Yang), and NIH/NCI (1R01CA20009, 5R01CA127258-05 and R21CA184788 to Q.P. Dou, and NIH P30 CA22453 to Karmanos Cancer Institute). HY Hsu was funded by grants from the Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 and NSC94-2314-B-320-002) and LT Lin was supported by a grant from Taipei Medical University (TMU101-AE3-Y19) NIH Grant K08 NS083732 to MDS is acknowledged. Dr. Gian Luigi Russo acknowledges the Fulbright Research Scholar program 2013-14. Work in CF''s lab described here was supported by Ministero dell{\textquoteright}Istruzione dell{\textquoteright}Universit{\`a} e della Ricerca (grant number: 200974K3JC). Dr. Clement G. Yedjou acknowledges NIH grant 5G12RR013459-13 through the RCMI-Center for Environmental Health at Jackson State University. Dr. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program {\textquoteleft}Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program: THALES (Grant number MIS 379346) and COST Action CM1201 {\textquoteleft}Biomimetic Radical Chemistry{\textquoteright}. The work reported by Nagi B. Kumar was funded by the National Institute of Health – National Cancer Institute R01 CA12060-01A1. Work in Carmela Famignori''s lab described here was supported by Ministero dell{\textquoteright}Istruzione dell{\textquoteright}Universit{\`a} e della Ricerca (grant number: 200974K3JC). Dr. Swapan K Ray and Mrinmay Chakrabarti acknowledge the support by United Soybean Board (USB Chesterfield, M, United States). The USB had no involvement in the writing of the manuscript or the decision to submit the manuscript for publication. Amr Amin was supported partially by Al-Jalila Foundation 2015, Zayed Center for Health Sciences 2015, and Terry Fox Foundation 2014. NIH grant 1 R21 CA188818 01A1 to Asfar Azmi is acknowledged. Funding Information: NIH Grants R21 1R21CA16984801 and 1R21CA17597401 to RMM is acknowledged. This work was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars and State Education Ministry and Scientific and Technological Innovation Project, Harbin ( 2012RFLXS011 to HJ Yang), and NIH/NCI ( 1R01CA20009 , 5R01CA127258-05 and R21CA184788 to Q.P. Dou, and NIH P30 CA22453 to Karmanos Cancer Institute). HY Hsu was funded by grants from the Ministry of Science and Technology of Taiwan ( NSC93-2314-B-320-006 and NSC94-2314-B-320-002 ) and LT Lin was supported by a grant from Taipei Medical University ( TMU101-AE3-Y19 ) NIH Grant K08 NS083732 to MDS is acknowledged. Dr. Gian Luigi Russo acknowledges the Fulbright Research Scholar program 2013-14. Work in CF's lab described here was supported by Ministero dell{\textquoteright}Istruzione dell{\textquoteright}Universit{\`a} e della Ricerca (grant number: 200974K3JC ). Dr. Clement G. Yedjou acknowledges NIH grant 5G12RR013459-13 through the RCMI-Center for Environmental Health at Jackson State University. Dr. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514 , Greek National funds through the Operational Program {\textquoteleft}Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program: THALES (Grant number MIS 379346 ) and COST Action CM1201 {\textquoteleft}Biomimetic Radical Chemistry{\textquoteright}. The work reported by Nagi B. Kumar was funded by the National Institute of Health – National Cancer Institute R01 CA12060-01A1 . Work in Carmela Famignori's lab described here was supported by Ministero dell{\textquoteright}Istruzione dell{\textquoteright}Universit{\`a} e della Ricerca (grant number: 200974K3JC ). Dr. Swapan K Ray and Mrinmay Chakrabarti acknowledge the support by United Soybean Board (USB Chesterfield, M, United States). The USB had no involvement in the writing of the manuscript or the decision to submit the manuscript for publication. Amr Amin was supported partially by Al-Jalila Foundation 2015, Zayed Center for Health Sciences 2015, and Terry Fox Foundation 2014. NIH grant 1 R21 CA188818 01A1 to Asfar Azmi is acknowledged. Funding Information: NIH Grants R21 1R21CA16984801 and 1R21CA17597401 to RMM is acknowledged. This work was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars and State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011 to HJ Yang), and NIH/NCI (1R01CA20009, 5R01CA127258-05 and R21CA184788 to Q.P. Dou, and NIH P30 CA22453 to Karmanos Cancer Institute). HY Hsu was funded by grants from the Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 and NSC94-2314-B-320-002) and LT Lin was supported by a grant from Taipei Medical University (TMU101-AE3-Y19) NIH Grant K08 NS083732 to MDS is acknowledged. Dr. Gian Luigi Russo acknowledges the Fulbright Research Scholar program 2013-14. Work in CF''s lab described here was supported by Ministero dell?Istruzione dell?Universit? e della Ricerca (grant number: 200974K3JC). Dr. Clement G. Yedjou acknowledges NIH grant 5G12RR013459-13 through the RCMI-Center for Environmental Health at Jackson State University. Dr. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program ?Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program: THALES (Grant number MIS 379346) and COST Action CM1201 ?Biomimetic Radical Chemistry?. The work reported by Nagi B. Kumar was funded by the National Institute of Health ? National Cancer Institute R01 CA12060-01A1. Work in Carmela Famignori''s lab described here was supported by Ministero dell?Istruzione dell?Universit? e della Ricerca (grant number: 200974K3JC). Dr. Swapan K Ray and Mrinmay Chakrabarti acknowledge the support by United Soybean Board (USB Chesterfield, M, United States). The USB had no involvement in the writing of the manuscript or the decision to submit the manuscript for publication. Amr Amin was supported partially by Al-Jalila Foundation 2015, Zayed Center for Health Sciences 2015, and Terry Fox Foundation 2014. NIH grant 1 R21 CA188818 01A1 to Asfar Azmi is acknowledged. Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",
year = "2015",
month = dec,
day = "1",
doi = "10.1016/j.semcancer.2015.03.001",
language = "English",
volume = "35",
pages = "S78--S103",
journal = "Seminars in Cancer Biology",
issn = "1044-579X",
publisher = "Academic Press Inc.",
}
