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Activation of Apoptosis Pathways by Anticancer Drugs

  • Chapter
Drug Resistance in Leukemia and Lymphoma III

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 457))

Abstract

The first antitumor drug (aminopterin) was introduced into the treatment of childhood leukemia by Sidney Farber almost 50 years ago. In the past 20 years long term remission and cure has been achieved in 70–80% of patients with leukemia, using combination therapy with several anticancer drugs and high dose protocols. However, the widespread use of chemotherapy also has shown that certain tumors are chemosensitive while others are chemoresistant. Why is chemotherapy effective? Anticancer drugs have not been designed for a specific cellular or molecular target but have been identified in assays based on their capacity to inhibit proliferation and clonogenicity. Early concepts on how chemotherapy may kill tumor cells have focused on interference with either cellular metabolism or DNA synthesis. However the biochemical characterization of drug mediated inhibition of cellular proliferation has shown that most drugs hit various targets. Drugs efficiently used in cancer therapy include diverse chemical compounds such as anti-metabolites (e.g. methotrexate, 5-fluorouracil), DNA damaging agents (e.g. cyclophosphamide, cisplatin, doxorubicine), mitotic inhibitors (e.g. vincristine), nucleotide analogs (6-mercaptopurine) or inhibitors of topoisomerases involved in DNA repair (e.g. etoposide). While cell death induced by anticancer agents has been considered to be a consequence of a block in proliferation or simply “toxicity”, recent studies have shown that most anticancer agents induce apoptosis in target cells.

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  1. University Children’s Hospital, Ulm, Germany

    Klaus-Michael Debatin

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  1. University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    G. J. L. Kaspers , R. Pieters  & A. J. P. Veerman ,  & 

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Debatin, KM. (1999). Activation of Apoptosis Pathways by Anticancer Drugs. In: Kaspers, G.J.L., Pieters, R., Veerman, A.J.P. (eds) Drug Resistance in Leukemia and Lymphoma III. Advances in Experimental Medicine and Biology, vol 457. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4811-9_25

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  • DOI: https://doi.org/10.1007/978-1-4615-4811-9_25

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