New target for Hepatocellular carcinoma therapy

Oct 25 2007

Hepatocellular carcinoma (HCC) is a major health problem worldwide. Currently, the only chance for obtaining a cure in patients with HCC is by either a surgical resection or liver transplantation.

However, many HCCs with scattered tumors cannot be operated on. In such patients, effective alternative therapies need to be discovered in order to treat patients in the early stages of this disease.

An article to be published on 28 October in the World Journal of Gastroenterology proposes a new target for therapy. A study was conducted by Dr. Satoshi Mamori, of Jikei University, in which he evaluated tumor biopsies in order to confirm the diagnosis of HCC.

The immunohistochemical expression of survivin in liver tumor specimens obtained from 17 patients was studied. In addition, to determine the survivin expression in response to anti-cancer drugs in early stage HCC, the survivin expression was determined after treating HCC cells with anti-cancer drugs under hypoxic culture conditions.

Survivin is a member of a family of inhibitors of apoptosis protein (IAP), which has been implicated in both the control of cell division and the inhibition of apoptosis. Survivin is selectively expressed in most common human neoplasms and it also appears to be involved in tumor cell resistance to some anticancer agents and ionizing radiation. Several preclinical studies have demonstrated a down-regulation of the survivin expression/function by the use of anti-sense oligonucleotide, dominant negative mutants, ribozymes, small interfering RNAs and cyclin-dependent kinase inhibitors to increase the rate of apoptosis, while also reducing the tumor growth potential and sensitized tumor cells to various chemotherapeutic drugs and ƒ×-irradiation using both in vitro and in vivo models of various types of human tumors.

The results and conclusions demonstrated survivin protein to be expressed in 64.7% of the cells in early HCC specimens (median). In early stage HCC with a tumor size > 10 mm, the expression rate ranged for 67.7 to 83.7%. Moreover, the survivin protein concentration in HCC cells increased with a combination of hypoxia and anti cancer drugs. With TACE, the conditions of hypoxia are maintained by embolisation over a long period of time. Therefore, this study suggests that survivin could be used as a potential useful therapeutic target for early HCC.