Targeting survival pathways in lymphoma

Luca Paoluzzi, Owen A. O'Connor

Research output: Chapter in Book/Report/Conference proceedingChapter

11 Scopus citations

Abstract

Abstract Targeting cellular death pathways including apoptosis is a promising strategy for cancer drug discovery. To date at least three major types of cell death have been distinguished, including: apoptosis, autophagy, and necrosis. Increasing evidence has begun to support a role of Bcl-2-family members in the cellular pathways involved in each of these processes. The induction of apoptosis in different types of tissue and in response to various stressors is a complex process that is controlled by different BCL-2 family members. Pharmacologic modulation of BCL-2 proteins and apoptosis can be achieved through different ways including the use of: (1) Modified peptides; (2) Small molecule inhibitors of anti-apoptotic proteins; (3) Antisense strategies; and (4) TRAIL targeting. Non-peptide based small-molecule inhibitors of signaling pathways are at present the strategy of choice given their low antigenicity and generally more favorable pharmacokinetic and pharmacodynamic features, especially as they pertain to volume of distribution and intracellular accumulation. Bcl2-family inhibitors are showing impressive preclinical efficacy in animal models and are moving rapidly towards phase I and II clinical trials. Appropriate preclinical studies will need to identify the optimal strategies for combining these agents, with an emphasis on the importance of dose and schedule dependency.

Original languageEnglish (US)
Title of host publicationBCL-2 Protein Family
Subtitle of host publicationEssential Regulators of Cell Death
EditorsClaudio Hetz, Claudio Hetz
Pages79-96
Number of pages18
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume687
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Paoluzzi, L., & O'Connor, O. A. (2010). Targeting survival pathways in lymphoma. In C. Hetz, & C. Hetz (Eds.), BCL-2 Protein Family: Essential Regulators of Cell Death (pp. 79-96). (Advances in Experimental Medicine and Biology; Vol. 687). https://doi.org/10.1007/978-1-4419-6706-0_5