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Mol Oncol. 2014 Sep 12;8(6):1067-83. doi: 10.1016/j.molonc.2014.05.004. Epub 2014 May 21.

Drug resistance to targeted therapies: déjà vu all over again.

Author information

1
Division of Molecular Carcinogenesis, Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
2
Division of Molecular Carcinogenesis, Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: r.bernards@nki.nl.

Abstract

A major limitation of targeted anticancer therapies is intrinsic or acquired resistance. This review emphasizes similarities in the mechanisms of resistance to endocrine therapies in breast cancer and those seen with the new generation of targeted cancer therapeutics. Resistance to single-agent cancer therapeutics is frequently the result of reactivation of the signaling pathway, indicating that a major limitation of targeted agents lies in their inability to fully block the cancer-relevant signaling pathway. The development of mechanism-based combinations of targeted therapies together with non-invasive molecular disease monitoring is a logical way forward to delay and ultimately overcome drug resistance development.

KEYWORDS:

Anticancer therapy; Drug combinations; Drug resistance; Endocrine therapy; Pathway reactivation; Targeted therapy

PMID:
24910388
PMCID:
PMC5528618
DOI:
10.1016/j.molonc.2014.05.004
[Indexed for MEDLINE]
Free PMC Article

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