Adaptive mechanisms of resistance to antineoplastic agents

Ferreira, Bibiana; Lie, Maria K.; Engelsen, Agnete S. T.; Machado, Susana; Link, Wolfgang; Lorens, James B.

http://hdl.handle.net/10400.1/13354

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Authors

Ferreira, Bibiana

Lie, Maria K.

Engelsen, Agnete S. T.

Machado, Susana

Link, Wolfgang

Lorens, James B.

Abstract(s)

Intrinsic and acquired resistance to conventional and targeted therapeutics is a fundamental reason for treatment failure in many cancer patients. Targeted approaches to overcome chemoresistance as well as resistance to targeted approaches require in depth understanding of the underlying molecular mechanisms. The anti-cancer activity of a drug can be limited by a broad variety of molecular events at different levels of drug action in a cell-autonomous and non-cell-autonomous manner. This review summarizes recent insights into the adaptive mechanisms used by tumours to resist therapy including cellular phenotypic plasticity, dynamic alterations of the tumour microenvironment, activation of redundant signal transduction pathways, modulation of drug target expression levels, and exploitation of pro-survival responses.

Keywords

To-mesenchymal transition Receptor tyrosine kinases Dna-damage response Breast-cancer Cclls Acute myelogenous leukemia Drug-resistance Tumor microenvironment Multidrug-resistance Ovarian-cancer Up-Rrulation