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Review

Growth factor receptors: promising drug targets in cancer

Snigdha Tiash, Ezharul Hoque Chowdhury
Jeffrey Cheah School of Medicine and Health Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, 46150 Bandar
Sunway, Selangor, Malaysia.
Correspondence to: Dr. Ezharul Hoque Chowdhury, Jeffrey Cheah School of Medicine and Health Sciences, Faculty of Medicine, Nursing and
Health Sciences, Monash University, 46150 Bandar Sunway, Selangor, Malaysia. E-mail: md.ezharul.hoque@monash.edu

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 signifi cant 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 fi ght the disease. Suitable nanocarriers capable of entrapping siRNA, mAb, GFR inhibitors and
classical drugs targeting GFR have potential therapeutic applications.
Key words: Carbonate apatite nanoparticles, growth factor receptor, monoclonal antibodies, protein kinase inhibitor, short
interfering RNA, tyrosine kinase inhibitor

Introduction Here, we have discussed the involvement of GFRs at
different stages of cancer progression and the molecular
The heterogeneous nature of cancer is characterized by therapeutic approaches to target GFRs.
continuous clonal expansion and uncontrolled growth
of mutated cells, intravasation and extravasation of GFR Involvement in Cancer Progression
blood and lymphatic vessels, dissemination, and
fi nally metastasis into distant organs. In the tumor Epidermal growth factor receptor
microenvironment, cells are supplied with nutrients by The epidermal growth factor receptor (EGFR)
the formation of disorganized blood vessels with leaky family encompasses four receptor proteins, namely
vasculature by the process of angiogenesis. Growth factor ErbB-1/EGFR-1 to -4 (also called HER 1-4) that are
receptors (GFRs), expressed on cell membranes or in the expressed on cell surface and exhibit tyrosine kinase
cytoplasm, have profound roles in cell growth, survival, activities. These proteins have similar structures and
angiogenesis and metastasis. Amplifi cation of GFRs are comprised of three domains: an extracellular
generates inherent and acquired resistance to classical domain with ligand binding site, a transmembrane
chemotherapies and targeted molecules. Escalated growth domain, and an intracellular domain with kinase
signals cross-talk differently with death signals to inhibit activity [Figure 1a]. There are 11 different growth
apoptosis that is programmed cell death. Accordingly, factors, each possessing a conserved EGF domain
signals mediated by GFRs function in collaboration to
enhance the complexity of the tumor microenvironment. This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
Access this article online the author is credited and the new creations are licensed under the identical
terms.
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How to cite this article: Tiash S, Chowdhury EH. Growth factor
receptors: promising drug targets in cancer. J Cancer Metastasis
DOI: Treat 2015;1:190-200.
10.4103/2394-4722.163151
Received: 06-02-2015; Accepted: 22-06-2015.

190 © 2015 Journal of Cancer Metastasis and Treatment ¦ Published by Wolters Kluwer - Medknow