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Breast Cancer Research
Published in: Breast Cancer Research 3/2001

01-06-2001 | Commentary

Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?

Authors: Guy Makin, Caroline Dive

Published in: Breast Cancer Research | Issue 3/2001

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Abstract

Drug resistance is a fundamental problem in the treatment of most common human cancers. Our understanding of the cellular mechanisms underlying death and survival has allowed the development of rational approaches to overcoming drug resistance. The mitogen activated protein kinase family of protein serine/threonine kinases has been implicated in this complex web of signalling, with some members acting to enhance death and other members to prevent it. A recent publication by MacKeigan et al is the first to demonstrate an enhancement of drug-induced cell death by simultaneous blockade of MEK-mediated survival signalling, and offers the potential for targeted adjuvant therapy as a means of overcoming drug resistance.
Literature
1.
Budman DR, Berry DA, Cirrincione CT, Henderson IC, Wood WC, Weiss RB, Ferree R, Muss HB, Green MR, Norton L, Frei E: Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. J Natl Cancer Inst. 1998, 90: 1205-1211. 10.1093/jnci/90.16.1205.CrossRefPubMed
2.
Raff MC: Social controls on cell survival and cell death. Nature. 1993, 356: 397-400. 10.1038/356397a0.CrossRef
3.
Hickman JA, Dive C: Apoptosis and Cancer Chemotherapy. Totowa, NJ: Humana Press,. 1999CrossRef
4.
5.
Zha JP, Harada H, Yang E, Jockel J, Korsmeyer SJ: Serine phosphorylation of death agonist Bad in response to survival factor results in binding to 14-3-3 not Bcl-X(L). Cell. 1996, 87: 619-628. 10.1016/S0092-8674(00)81382-3.CrossRefPubMed
6.
Dijkers PF, Medema RH, Lammers J-WJ, Koenderman L, Coffer PJ: Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr Biol. 2000, 10: 1201-1204. 10.1016/S0960-9822(00)00728-4.CrossRefPubMed
7.
Taylor ST, Hickman JA, Dive C: Epigenetic determinants of resistance to etoposide regulation of Bcl-x(L) and Bax by tumor microenvironmental factors. J Natl Cancer Inst. 2000, 92: 18-23. 10.1093/jnci/92.1.18.CrossRefPubMed
8.
Gilmore AP, Metcalfe AD, Romer LH, Streuli CH: Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization. J Cell Biol. 2000, 149: 431-445. 10.1083/jcb.149.2.431.CrossRefPubMedPubMedCentral
9.
Ghatan S, Larner S, Kinoshita Y, Hetman M, Patel L, Xia Z, Youle RJ, Morrison RS: p38 MAP kinase mediates Bax translocation in nitric oxide-induced apoptosis in neurons. J Cell Biol. 2000, 150: 335-347. 10.1083/jcb.150.2.335.CrossRefPubMedPubMedCentral
10.
Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, BarSagi D, Jones SN, Flavell RA, Davis RJ: Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science. 2000, 288: 870-874. 10.1126/science.288.5467.870.CrossRefPubMed
11.
English J, Pearson G, Wilsbacher J, Swantek J, Karandikar M, Xu S, Cobb MH: New insights into the control of MAP kinase pathways. Exp Cell Res. 1999, 253: 255-270. 10.1006/excr.1999.4687.CrossRefPubMed
12.
Derijard B, Raingeaud J, Barrett T, Wu I-H, Han J, Ulevitch RJ, Davis RJ: Independant human MAP kinase signal transduction pathways defined by MEK and MKK isoforms. Science. 1995, 267: 682-685.CrossRefPubMed
13.
Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995, 270: 1326-1331.CrossRefPubMed
14.
Yang DD, Kuan CY, Whitmarsh AJ, Rincon M, Zheng TS, Davis RJ, Rakic P, Flavell RA: Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature. 1997, 389: 865-870. 10.1038/39899.CrossRefPubMed
15.
Rincon M, Whitmarsh A, Yang DD, Weiss L, Derijard B, Jayaraj P, Davis RJ, Flavell RA: The JNK pathway regulates the in vivo deletion of immature CD4+CD8+ thymocytes. J Exp Med. 1998, 188: 1817-1830. 10.1084/jem.188.10.1817.CrossRefPubMedPubMedCentral
16.
Yujiri T, Sather S, Fanger GR, Johnson GL: Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption. Science. 1998, 282: 1911-1914. 10.1126/science.282.5395.1911.CrossRefPubMed
17.
Natoli G, Costanzo A, Ianni A, Templeton DJ, Woodgett JR, Balsano C, Levrero M: Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. Science. 1997, 275: 200-203. 10.1126/science.275.5297.200.CrossRefPubMed
18.
Dudley DT, Pang L, Decker SJ, Bridges AJ, Saltiel AR: A synthetic inhibitor of the mitogen activated protein kinase cascade. Proc Natl Acad Sci USA. 1995, 92: 7686-7689.CrossRefPubMedPubMedCentral
19.
Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F, Copeland RA, Magolda RL, Scherle PA, Trzaskos JM: Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem. 1998, 273: 18623-18632. 10.1074/jbc.273.29.18623.CrossRefPubMed
20.
Sebolt-Leopold JS, Dudley DT, Herrera R, Becelare KV, Wiland A, Gowan RC, Tecle H, Barrett SD, Bridges A, Przybranowski S, Leopold WR, Saltiel AR: Blockade of the MAP kinase pathway suppresses growth of colon tumours in vivo. Nat Med. 1999, 5: 810-816. 10.1038/10533.CrossRefPubMed
21.
Sivaraman VS, Wang H, Nuovo GJ, Malbon CC: Hyperexpression of mitogen activated protein kinase in human breast tissue. J Clin Invest. 1997, 99: 1478-1483.CrossRefPubMedPubMedCentral
22.
Jordan MA, Toso RJ, Thrower D, Wilson L: Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci USA. 1993, 90: 9552-9556.CrossRefPubMedPubMedCentral
23.
Amato SF, Swart JM, Berg M, Wanebo HJ, Mehta SR, Chiles TC: Transient stimulation of the c-Jun-NH2-terminal kinase/activator protein 1 pathway and inhibition of extracellular signal-related kinase are early events in paclitaxel-mediated apoptosis in human B lymphoblasts. Cancer Res. 1998, 58: 241-247.PubMed
24.
Maundrell K, Antonsson B, Magnenat E, Camps M, Muda M, Chabert C, Gillieron C, Boschert U, Vial-Knecht E, Martinou J-C, Arkinstall S: Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Rac1. J Biol Chem. 1997, 272: 25238-25242. 10.1074/jbc.272.40.25238.CrossRefPubMed
25.
MacKeigan JP, Collins TS, Ting JP-Y: MEK inhibition enhances paclitaxel-induced tumor apoptosis. J Biol Chem. 2000, 275: 38953-38956. 10.1074/jbc.C000684200.CrossRefPubMed
Metadata
Title
Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?
Authors
Guy Makin
Caroline Dive
Publication date
01-06-2001
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2001
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr289

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