Growth factor receptors: promising drug targets in cancer

Abstract

Genetic, epigenetic and somatic changes deregulate the expression of growth factor receptors (GFRs), leading to cancer initiation and progression. Tumor cell growth and survival are orchestrated by clonal expansion and evasion of apoptotic signals in cancer cells. The growth of cells is further supported by angiogenesis and metastasis to distant organs. High expression of GFRs also contributes to the development of resistance. Therefore, therapeutics to target GFRs is a potentially attractive molecular approach to treat cancer more effectively. In this review, we have discussed the contribution of GFRs to cancer development and addressed molecular approaches undertaken to inhibit GFR-mediated pathways. A wide number of monoclonal antibodies (mAbs) and protein kinase inhibitors targeting these GFR-mediated functions are in clinical trials to treat human malignancies. However, most drugs that target GFRs lead to the development of drug resistance and generate adverse effects. Nucleic acid-based therapeutics, e.g. short interfering RNA (siRNA) could be harnessed to selectively silence GFR genes in cancer cells. Different polymer, liposome-based nanocarriers, and the most recently developed pH-sensitive inorganic carbonate apatite nanoparticles have been used in cell culture and preclinical trials for cytoplasmic delivery of the siRNAs targeting different GFR genes. siRNA-based therapeutics have been shown to have significant potential to suppress GFR expression and functions and thus could be developed as molecular therapeutics. Multi-targeting of tumors at different levels by combining various approaches along with chemotherapy would be a promising therapeutic approach to fight the disease. Suitable nanocarriers capable of entrapping siRNA, mAb, GFR inhibitors and classical drugs targeting GFR have potential therapeutic applications.

Keywords

Carbonate apatite nanoparticles / growth factor receptor / monoclonal antibodies / protein kinase inhibitor / short interfering RNA / tyrosine kinase inhibitor

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