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ONYX-015. Onyx Pharmaceuticals.

E E Cohen1, C M Rudin

  • 1Section of Hematology/Oncology, University of Chicago Medical Center, IL 60637, USA. crudin@medicine.bsd.uchicago.edu

Current Opinion in Investigational Drugs (London, England : 2000)
|March 15, 2002
PubMed
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ONYX-015 is a novel oncolytic adenovirus designed to target cancer cells with p53 mutations, sparing normal cells. This targeted viral therapy shows promise for treating various solid tumors, including head and neck cancers.

Area of Science:

  • Oncolytic virotherapy
  • Cancer genetics
  • Viral oncology

Background:

  • Mutations in the p53 tumor suppressor gene are prevalent in over half of human cancers.
  • Wild-type adenoviruses require p53 inactivation for replication, making them ineffective against p53-mutated cancer cells.
  • ONYX-015 is a modified adenovirus engineered to selectively replicate in and destroy cancer cells with p53 loss-of-function mutations.

Purpose of the Study:

  • To evaluate the therapeutic potential of ONYX-015 (CI-1042) as a targeted cancer treatment.
  • To investigate the selective replication and oncolytic activity of ONYX-015 in p53-mutated cancer cells.
  • To review the ongoing clinical trial status and patent landscape for ONYX-015.

Main Methods:

  • Development of a recombinant adenovirus (ONYX-015) with a loss-of-function mutation in the E1B gene, preventing p53 inactivation.

Related Experiment Videos

  • Selective viral replication and cell lysis in cancer cells harboring p53 mutations.
  • Clinical trials (Phase I, II, and III) across various solid tumor types, including head and neck, gastrointestinal, pancreatic, colorectal, ovarian, and liver cancers.

    • Main Results:

    • ONYX-015 demonstrates selective replication in cancer cells with p53 mutations, leading to cell death.
    • Normal cells with functional p53 remain largely unaffected by ONYX-015.
    • Ongoing clinical trials are evaluating its efficacy in recurrent head and neck cancer and other solid tumors.

    Conclusions:

    • ONYX-015 represents a promising targeted therapy for cancers with p53 mutations.
    • Its oncolytic mechanism offers a potential treatment strategy with reduced toxicity to normal tissues.
    • Onyx Pharmaceuticals holds key patents covering the use of modified adenoviruses for treating p53-deficient cancers.