Targeting tumour-supportive cellular machineries in anticancer drug development

doi:10.1038/nrd4201

Review

. 2014 Mar;13(3):179-96.

doi: 10.1038/nrd4201.

Targeting tumour-supportive cellular machineries in anticancer drug development

Matthias Dobbelstein¹, Ute Moll²

Affiliations

¹ Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany.
² 1] Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany. [2] Department of Pathology, School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.

PMID: 24577400
DOI: 10.1038/nrd4201

Review

Targeting tumour-supportive cellular machineries in anticancer drug development

Matthias Dobbelstein et al. Nat Rev Drug Discov. 2014 Mar.

. 2014 Mar;13(3):179-96.

doi: 10.1038/nrd4201.

Authors

Matthias Dobbelstein¹, Ute Moll²

Affiliations

¹ Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany.
² 1] Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany. [2] Department of Pathology, School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.

PMID: 24577400
DOI: 10.1038/nrd4201

Abstract

Traditional anticancer chemotherapeutics targeting DNA replication and cell division have severe side effects, but they have proved to be highly successful in treating some cancers. Drugs targeting signalling oncoproteins that have gained tumour-driving functions through mutations or overexpression were subsequently developed to increase specificity and thus reduce side effects, but have limitations such as the development of resistance. Now, a new wave of small-molecule anticancer agents is emerging, targeting complex multicomponent cellular machineries - including chromatin modifiers, heat shock protein chaperones and the proteasome - which thus interfere with those support systems that are more essential for cancer cells than for normal cells. Here, we provide our perspective on the advantages and limitations of agents that target tumour-supportive cellular machineries (other than those involving DNA replication), comparing them with agents that target signalling intermediates.

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[1] Clin Cancer Res. 2012 Apr 1;18(7):1824-6 - PubMed

[2] Clin Cancer Res. 2012 Apr 1;18(7):1824-6 - PubMed

[3] Nat Rev Cancer. 2006 Jan;6(1):38-51 - PubMed

[4] Nat Rev Cancer. 2006 Jan;6(1):38-51 - PubMed

[5] Nat Med. 2011 Dec 11;18(1):74-82 - PubMed

[6] Nat Med. 2011 Dec 11;18(1):74-82 - PubMed

[7] Nat Rev Cancer. 2010 Apr;10(4):293-301 - PubMed

[8] Nat Rev Cancer. 2010 Apr;10(4):293-301 - PubMed

[9] Cancer Chemother Pharmacol. 2011 Jan;67 Suppl 1:S15-24 - PubMed

[10] Cancer Chemother Pharmacol. 2011 Jan;67 Suppl 1:S15-24 - PubMed

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Targeting tumour-supportive cellular machineries in anticancer drug development

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Targeting tumour-supportive cellular machineries in anticancer drug development

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