Pharmaceutical composition and pharmaceutical kit for the treatment of hepatocellular carcinoma

Pharmaceutical composition comprising a Notch3 inhibitor, an anti-tumoral chemotherapeutic agent and pharmaceutical acceptable carriers, for the treatment of Hepatocellular Carcinoma.

Title of the patent Pharmaceutical composition and pharmaceutical kit for the treatment of hepatocellular carcinoma
Thematic area Pharmaceutical
Ownership Alma Mater Studiorum - Università di Bologna
Inventors Luigi Bolondi, Catia Giovannini, Pasquale Chieco, Kenneth Marcu
Protection Canada, Japan, USA, Australia, Europe, China
Licensing status Available for licensing agreement
Keywords Hepatocellular carcinoma, Notch3, shRNA, doxorubicin, cell death
Filed on Jul 25, 2007

Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide among all human cancer and causes 1 million deaths annually. Despite many promising treatment options, which include surgical resection, alcohol or radiofrequency ablation, chemoembolization and liver transplantation, long-term prognosis remains poor in patients with advanced disease. Notch genes encode for a family of highly conserved single-pass transmembrane receptors known as Notch1, 2, 3 and 4. Because of increasing evidence that Notch signaling pathway is deregulated in different human tumours, Notch receptors have become targets for killing malignant cells.

The invention provides pharmaceutical composition for the treatment of hepatocellular carcinoma (HCC) comprising Notch3 inhibitors and chemotherapeutic agent, methods for the preparation of said composition and medical treatment comprising its administration in patients in need thereof. The invention investigates Notch3 protein expression in paired samples of HCC and adjacent HCC free human liver specimens using immunohistochemistry.

  • In vitro Notch3 depletion tripled the apoptosis inducing effect of a chemotherapeutic agent after 24 hour of treatment;
  • Notch3 specific inhibitors could be developed for the treatment of human HCC