A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one or more ErbB ligands correlates with decreased patient survival. The currently approved drugs for the treatment of cancers driven by the ErbB family target the receptors rather than the ligands, and they include either monoclonal anti-receptor antibodies, or tyrosine kinase inhibitors (TKIs). Because of resistance and moderate clinical efficacies of anti-receptor antibodies and TKIs it is worthwhile considering alternative strategies. The present technology combines several antibodies, capable of blocking ErbB ligands, with chemotherapy.
- Treatment of cancers that possess the ErbB receptors (e.g. colorectal, liver, bladder, and head and neck tumors)
- Effective blockade of the tumorigenic action of ErbB-specific ligands
- The combination protocol may enhance the sensitivity to chemotherapy
In the outlined technology, monoclonal antibodies were generated against two ligands, namely TGF-? and heparin-binding EGF-like growth factor. Combining the two antibodies with a chemotherapeutic drug enhanced the ability of chemotherapy to inhibit pancreatic tumors in mice. Therefore, this technology offers a general cancer therapeutic strategy that entails profiling the repertoire of growth factors secreted by a tumor, and combining with chemotherapy several antibodies capable of blocking autocrine ligands, in a way that sensitizes tumors to cytotoxicity and delays onset of chemoresistance.