From old alkylating agents to new minor groove binders

Abstract Alkylating agents represent the oldest class of anticancer agents with the approval of mechloretamine by the FDA in 1949. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in the treatment of specific malignancies, sometimes repr...

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Bibliographic Details
Published in:Critical reviews in oncology/hematology 2014-01, Vol.89 (1), p.43-61
Main Authors: Puyo, Stéphane, Montaudon, Danièle, Pourquier, Philippe
Format: Article
Language:English
Subjects:
Alkylating agents
Alkylating Agents - chemistry
Alkylating Agents - metabolism
Alkylating Agents - pharmacology
Alkylating Agents - therapeutic use
Alkylation
Animals
Antineoplastic Agents, Alkylating - chemistry
Antineoplastic Agents, Alkylating - metabolism
Antineoplastic Agents, Alkylating - pharmacology
Antineoplastic Agents, Alkylating - therapeutic use
DNA - chemistry
DNA - metabolism
DNA adducts
DNA crosslinks
DNA repair
Drug Resistance, Neoplasm
Hematology, Oncology and Palliative Medicine
Humans
Life Sciences
Neoplasms - drug therapy
Neoplasms - metabolism
O6-methylguanine
Signal Transduction - drug effects
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Summary:Abstract Alkylating agents represent the oldest class of anticancer agents with the approval of mechloretamine by the FDA in 1949. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in the treatment of specific malignancies, sometimes representing the unique option for the treatment of refractory tumors. Here, we are reviewing the major classes of alkylating agents, with a particular focus on the latest generations of compounds that specifically target the minor groove of the DNA. These naturally occurring derivatives have a unique mechanism of action that explains the recent regain of interest in developing new classes of alkylating agents that could be used in combination with other anticancer drugs to enhance tumor response in the clinic.
ISSN:1040-8428
1879-0461
DOI:10.1016/j.critrevonc.2013.07.006