Cancer Research - Europa

OVCAD
Ovarian Cancer – Diagnosis of
a Silent Killer
Summary
In Europe each year, 63 000 ovarian cancer cases are diagnosed
and 41 000 ovarian cancer patients die. Seventy-fi ve
per cent of patients are diagnosed at advanced stages due
to an asymptomatic course and 75 % of these patients die
within fi ve years. Treatment involves surgery followed by
chemotherapy. However, 25 % of patients relapse within six
months after initial treatment and there is doubt as to
whether these patients benefi t from this therapy at all.
Recurrent disease is diagnosed by clinical evidences or by
CA125 dynamics. But detection is limited due to a lack of
sensitivity and specifi city, as is the case with primary
diagnosis.
Currently, there is no method to detect minimal disease, the
fi rst indicator of therapy failure and a precursor of recurrence,
which inevitably leaves specifi c traces throughout
the body. There is a strong need for molecular-oriented
research to detect minimal disease in order to disburden
patients from an ineffi cient and toxic therapy.
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Keywords | Ovarian cancer | molecular diagnosis | minimal disease | chemotherapy | gene expression | signature |
proteomics | CGH | mutation | methylation | targeted therapy |
Ovarian carcinoma – immunohistochemical staining of L1on ovarian carcinoma and its
metastases in adjacent organs (Source: J. Sehouli, Berlin; M. Fogel, Rehovot and P. Altevogt,
Heidelberg).
Problem
Diagnosis at advanced stages and a high mortality rate is
the tragedy of ovarian cancer. After initial surgical therapy,
25 % of patients relapse within six months and 75 % die within
fi ve years, mainly due to resistance to chemotherapy.
Available methods for the detection of recurrent disease
lack both sensitivity and specifi city and usually miss minimal
disease as a fi rst sign of therapy resistance.
Aim
The aim of this project is to defi ne clinically useful molecular-orientated
early detection of minimal residual disease
(MRD) in ovarian cancer that can identify patients not
responding to the standard (state-of-theart) therapy at the
time of surgery. This will disburden the patients from the
very toxic and ineffi cient standard chemotherapy and eventually
lead to alternative therapy modalities, which can really
bring benefi ts to this group of patients. ‘Signatures’ that signal
the presence of MRD will be investigated at various
molecular levels (DNA, RNA and protein) and in a broad
spectrum of biological materials (tumour tissue, disseminated
tumour cells, sera, white blood cells, ascites) from ovarian
cancer patients.
Specifi cally, the project is aiming at:
• development and/or validation of several molecular
diagnostic methods to identify MRD in ovarian cancer
patients;
• defi nition of a new ‘diagnostic state-of-the-art’ by correlating
the diagnostic results with the clinically-defi ned
response of the patients to standard therapy, consisting
of primary surgery, followed by standard platinum/Taxolbased
chemotherapy;
• early discovery and characterisation of MRD by molecular
diagnostics leading to additional therapeutic interventions,
ultimately improving patients’ prognosis and quality
of life;
• better understanding of the mechanisms that cause
MRD and therapy failure;
• identifi cation and evaluation of new potential therapy
targets.
Expected results
Defi nition of a diagnostic method consisting of one or several
molecular tests for early detection of minimal disease as
an early indicator of therapy failure.
Potential applications
Diagnostic molecular tests and immunotherapy.
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME