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