Monoclonal Antibodies

The signaling pathways controlling cell growth and differentiation are almost invariably altered in cancer and the metastatic spread of primary tumours to other organs is facilitated by many signaling pathways. Comprehensive maps of protein networks will lead to identification of nodal signaling protein motifs and open up avenues for better therapeutic intervention strategies. Immune-mediated tumour cell killing can be carried out by an antibody binding to a cell surface receptor and blocking dimerization, kinase activation and downstream signaling, leading to reduced proliferation and apoptosis or an antibody binding to an enzyme leading to neutralization, signaling abrogation and cell death¹.

Deciphering these interconnected signaling pathways is leading to the development of monoclonal antibody cancer drugs. For example, the observation that the epidermal growth factor receptor-2 (ERBB2) gene is amplified, and that its encoded receptor protein is aberrantly expressed in some breast cancers triggered the development of trastuzumab (Herceptin), which is an effective antibody therapy. Bevacizumab (Avastin), which is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF) receptor, is an example of an angiogenesis signaling pathway-targeted therapy that has shown some efficacy in the treatment of colorectal cancers. The dependence of many prostate tumour cells on androgen receptor (AR) signalling, which is required for the survival of normal prostate secretory epithelial cells, and the therapeutic efficacy of AR antagonists are further examples of the validity of these concepts².