A new tumor
suppressor and a new treatment using an old drug: Promises in better
understanding and treatment of a lethal tumor.
Patients
with advanced liver disease - in particular when due to hepatitis B or
C are at risk to develop hepatocellular carcinoma (HCC). Its incidence
is increasing: The mortality due HCC has nearly doubled in the last
decade. Unfortunately, the potential for curative treatment remains
limited. Therefore, new avenues of research need to be explored; my
laboratory is attacking this problem on two levels:
- To define new fundamental pathways
underlying the development of HCC
- Ameliorate treatment by
cutting the blood supply to the tumor taking advantage of the dramatic
progresses made in other forms of cancer.
The more fundamental approach
led to discovery of a new protein.Low expression of this protein in
tumor predicts poor survival. It is located in the organelles
responsible for providing the liver cells with energy, the
mitochondria). There it is involved in the metabolism of an important
nucleic acid , namely adenosine (which in turn is a building block of
DNA). Reducing its level of expression is associated with a stronger
resistance to certain lethal stresses thereby conveying a survival
advantate to the tumor cell. We try to understand the role of this
protein in cancer using high-throughput technologies (microarrays and
proteomics) as well as using animals engineered to lack this protein.
To evaluate novel forms of
treatment, we use an experimental model of HCC in the rat; tumor growth
is measured by MR imaging. We found that a set of drugs already used to
prevent rejection after liver transplantation can slow progression of
the tumor and to significantly improve the survival of the animals.
This is mainly due to the inhibition of the formation of new blood
vessels thereby depriving the tumor of oxygen and nutrients. This
approach leads to even more dramatic effects when combined with
conventional chemotherapy. This approach will soon be investigated in
clinical trials; this offers a chance to the many patients who cannot
benefit from curative treatments.
Growth of HCC in the rat as followed by MRT
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