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Alkylating Agents

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Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures

Part of the book series: Cancer Growth and Progression ((CAGP,volume 13))

Abstract

Alkylating agents were the first anticancer molecules developed and are still used today. The family contains 6 major classes: nitrogen mustards, aziridines, alkyl sulfonates, epoxides, nitrosoureas and triazene compounds. Due to their chemical properties, these drugs can, either directly or after biological activation react and form covalent bonds with macromolecules such as DNA, RNA and proteins. Their cytotoxic properties are mainly associated with their capacity to induce DNA damage and trigger cell death. Various mechanisms of resistance to these drugs, including augmented DNA repair and increased detoxification by glutathione and glutathione-related enzymes have been described. The use of alkylating agents is limited by their deleterious side effects, including hematopoietic suppression. In order to overcome these important clinical issues, new generations of alkylating agents which are preferentially activated by tumor cells have been developed. Among those, TLK286, a glutathione S-transferase P1–1 activated prodrug that elicits cytotoxicity against cancer cells but has bone marrow sparing activities, is one example. This compound may be a forerunner of new anticancer drugs that will make chemotherapy more efficient and safer for patients.

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  1. INRS, 54000, Nancy, France

    Laurent Gate

  2. Department of Pharmacology, 173 Ashley Ave, Charleston, SC, 29466, USA

    Kenneth D. Tew

  3. Department of Pharmacology, Medical University South Carolina, 173 Ashley Ave, Charleston, SC, 29466, USA

    Kenneth D. Tew

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    Boris R. Minev

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Gate, L., Tew, K.D. (2011). Alkylating Agents. In: Minev, B. (eds) Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures. Cancer Growth and Progression, vol 13. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9704-0_4

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