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Biersack. Cancer Drug Resist 2019;2:1-17 Cancer
DOI: 10.20517/cdr.2019.09 Drug Resistance

Review Open Access

Alkylating anticancer agents and their relations to
microRNAs

Bernhard Biersack
Organic Chemistry Laboratory, University of Bayreuth, Bayreuth 95440, Germany.

Correspondence to: Dr. Bernhard Biersack, Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30,
Bayreuth 95440, Germany. E-mail: bernhard.biersack@uni-bayreuth.de

How to cite this article: Biersack B. Alkylating anticancer agents and their relations to microRNAs. Cancer Drug Resist 2019;2:1-17.
http://dx.doi.org/10.20517/cdr.2019.09

Received: 15 Dec 2018 First Decision: 18 Dec 2018 Revised: 17 Jan 2019 Accepted: 25 Jan 2019 Published: 19 Mar 2019
Science Editor: Aamir Ahmad Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Alkylating agents represent an important class of anticancer drugs. The occurrence and emergence of tumor resistance
to the treatment with alkylating agents denotes a severe problem in the clinics. A detailed understanding of the
mechanisms of activity of alkylating drugs is essential in order to overcome drug resistance. In particular, the role of non-
coding microRNAs concerning alkylating drug activity and resistance in various cancers is highlighted in this review. Both
synthetic and natural alkylating agents, which are approved for cancer therapy, are discussed concerning their interplay
with microRNAs.

Keywords: Alkylating agents, microRNA, anticancer agents, DNA, drug resistance

INTRODUCTION
Alkylating agents represent an important tool for the daily fight against cancer. Interestingly, their
introduction into clinical application based on chemical warfare. Like a knife that can kill in the hands of
an assassin and heal in the hands of a surgeon, the potential of nitrogen and sulfur mustards as anticancer
agents was identified after incidents with poison gas (reduction of white blood cells) during World War II and
[1,2]
dates back to observations after poison gas attacks during World War I . Rational chemical modifications
led to less lethal anticancer drug candidates such as melphalan, chlorambucil, and cyclophosphamide (all
of them are nitrogen mustards). Alkylation of bionucleophiles (proteins, nucleic acids) mainly occurs at N,
O, and S sites with free electron pairs. In most cases DNA was identified as the main target of alkylating
agents and both mono-functional (reaction with only one DNA strand) and bifunctional alkylating agents
[2]
(reaction with two strands leading to DNA crosslinks) are known . Pertinent drug resistance strategies of

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