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Small-molecule Bcl-2 antagonists as targeted therapy in oncology

M R Warr, G C Shore

    Current Oncology (Toronto, Ont.)
    |December 17, 2008
    PubMed

    Insights

    Cancer cells often evade apoptosis by upregulating pro-survival Bcl-2 proteins, leading to therapy resistance. Small-molecule Bcl-2 antagonists offer a strategy to overcome this block and selectively kill cancer cells.

    Area of Science:

    • Molecular Biology
    • Cancer Biology
    • Drug Discovery

    Background:

    • Pro-survival Bcl-2 proteins are upregulated in cancer cells, blocking apoptosis.
    • This upregulation contributes to resistance against conventional cancer chemotherapeutics.
    • Targeting pro-survival Bcl-2 proteins can overcome apoptosis resistance.

    Purpose of the Study:

    • To review the progress of small-molecule Bcl-2 antagonists in clinical trials.
    • To highlight strategies for alleviating apoptosis blocks in cancer cells.
    • To discuss the potential of Bcl-2 antagonists in cancer therapy.

    Main Methods:

    • Review of clinical trial data for small-molecule Bcl-2 antagonists.
    • Analysis of Bcl-2 family protein interactions in apoptosis regulation.
    • Discussion of cancer cell survival mechanisms and therapeutic resistance.

    Main Results:

    • Three small-molecule Bcl-2 antagonists have advanced into clinical evaluation.
    • These antagonists aim to inactivate pro-survival Bcl-2 family members.
    • Targeting Bcl-2 proteins offers a potential strategy to selectively kill cancer cells.

    Conclusions:

    • Small-molecule Bcl-2 antagonists represent a promising therapeutic strategy.
    • Overcoming the apoptosis block in cancer cells can enhance treatment efficacy.
    • Selective killing of malignant cells is achievable by targeting pro-survival pathways.
    Keywords:
    ApoptosisBcl-2

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