Next Generation of Investigational Anti-Cancer Agents Unveiled at ASCO by AstraZeneca


    ALDERLEY PARK, England, June 4 /CNW/ - AstraZeneca (LSE: AZN; NYSE:   AZN)
today announced details of two new investigational cancer therapies at the
American Society of Clinical Oncology (ASCO) meeting.
    AZD2281 (KU-0059436) is a small molecule inhibitor of Poly-ADP Ribose
Polymerase (PARP). PARP is an enzyme involved in Base Excision Repair which is
a key pathway in the repair of DNA single-stranded breaks. Inhibiting this DNA
repair mechanism, in tandem with a defective DNA repair gene like BRCA1 or
BRCA2, is thought to lead to double-stranded DNA breaks that tumour cells are
unable to repair, resulting in tumour cell death.
    AZD2281 has been studied in a range of tumour types in Phase I studies.
The study presented at ASCO showed that treatment with AZD2281 led to
inhibition of PARP functional activity in both surrogate and tumor tissue, and
reported that strong signals were detected in hereditary ovarian cancer.
    Between 5% and 10% of all breast and ovarian cancers are believed to be
associated with mutations in the BRCA1 or BRCA2 mutations. Women with BRCA
mutations are reported to have up to an 87% risk of developing breast cancer,
and up to a 44% risk of developing ovarian cancer by the age of 70.
    Professor James Carmichael of AstraZeneca said: "We are delighted to be
working with The Royal Marsden Hospital and Netherlands Cancer Institute (NKI)
on this study, which is at the forefront of research into new targeted
treatments for cancer. We have seen promising early results in patients with
hereditary ovarian cancer, which have encouraged us to move rapidly into the
next phase of development for this compound."
    AZD0530, another investigational compound in Phase II clinical
development is an inhibitor of Src in tumours. Src was the first
cancer-causing gene to be discovered in the 1970s. Src kinases are a family of
molecules that play an important role in cancer growth, spread, apoptosis and
cell proliferation. By inhibiting Src it is hoped that cancer progression may
be delayed.
    Preclinical studies have identified AZD0530 as a selective inhibitor of
Src activity. In the study data presented today, biomarkers confirmed
inhibition of Src in human cancers for the first time.
    Principal Investigator for the study(1) presented at ASCO, Jose Baselga
MD, Chairman and Professor of Medicine, Vall d'Hebron University Hospital,
Barcelona, Spain commented: "Through inhibiting Src in preclinical studies,
AZD0530 has shown promise to target a wide range of tumors and has the
potential to be used in patients with either early or advanced cancers.
    AZD0530 offers a 'multi-mechanistic' approach to fighting cancer, meaning
it not only delays tumour spread but has additional potential to treat tumours
that have spread to patients' bones, enhance the efficacy of many standard
cancer therapies and to treat leukemia."
    Highlighting the advantage of this study for patients, he added, "The
AZD0530 clinical trial program was exceptionally well-designed allowing full
evaluation of the optimal methodology for measuring Src activation prior
measuring its inhibition by AZD0530. By collecting as much information early
on in our clinical trials we give ourselves the best chance of identifying
those patients who could benefit most from treatment with AZD0530 in the

    /Notes to Editors:

    - Both of these studies were presented at oral sessions at ASCO 2007.

    - An ASCO merit award was given for the AZD2281 presentation (First in
human phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of
KU-0059436 (Ku), a small molecule inhibitor of Poly ADP-Ribose Polymerase
(PARP) in cancer patients (p), including BRCA1/2 mutation carriers).

    - AstraZeneca is a major international healthcare business engaged in the
research, development, manufacture and marketing of prescription
pharmaceuticals and the supply of healthcare services. It is one of the
world's leading pharmaceutical companies with healthcare sales of
US$26.47 billion and leading positions in sales of gastrointestinal,
cardiovascular, neuroscience, respiratory, oncology and infection products.

    AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as
well as the FTSE4 Good Index.

    - For more information about AstraZeneca, please visit:

    - KuDOS Pharmaceuticals Ltd is a wholly-owned subsidiary of AstraZeneca.
AstraZeneca acquired KuDOS Pharmaceuticals in Feb 2006. KuDOS research is
focused on the discovery of molecules to treat cancer in the area of DNA
repair inhibition.

    (1) Phase I study of AZD0530, an oral potent inhibitor of Src kinase:
    first demonstration of inhibition of Src activity in human cancers/

For further information:

For further information: please contact: Carrie Deverell,, Mobile: +44(0)-7929-845108

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