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

Alderley Park, England (ots/PRNewswire)

- FOR NON-US/NON-UK MEDICAL MEDIA ONLY
ALDERLEY PARK, England, June 4 /PRNewswire/ --
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 future."
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: www.astrazeneca.com
  • 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

Contact:

For further information, please contact: Carrie Deverell,
carrie.deverell@astrazeneca.com, Mobile: +44(0)-7929-845108

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