Biomedical Potentials Of Calcitonin Gene-relate Peptide (CGRP) Antagonist In The Control Of Prostate Cancer And Its Bone Metastasis In Adult Males: A Review | 99618
Journal of Cancer Science & Therapy
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Calcitonin gene-related peptide (CGRP) is a 37 amino acid regulatory neuropeptide derived from alternative splicing of the
calcitonin/CGRP gene. It is primarily localized to C and A-delta sensory fibers which display wide innervations throughout the
body. It has been suggested that CGRP, as well as its antagonist, have wide potential as the therapy for treating many diseases depending
on the biochemical pathway mobilized by each of them. Nevertheless, limited progress has hitherto been made in these areas. The
development of CGRP antagonists has remarkably shown that CGRP antagonists have great potential in the management of pain.
Receptors for calcitonin family including calcitonin, CGRP and Amylin, adrenomedullin (AM) are formed by two separate proteins,
a seven transmembrane domain G protein-coupled receptor and a receptor activity modifying protein (RAMP). The calcitonin family
and their receptors have a wide range of physiological and pathological functions of which the promotions of tumourigenesis across
many different cancer types stand out. For many years, the calcitonin-calcitonin receptor axis has been shown to be important in
many malignant diseases. Activation of the calcitonin gene-related peptide and its receptors axis stimulates invasion, angiogenesis,
chemoresistance and metastasis in many cancer cell lines including prostate cancer cells. Calcitonin gene-related peptide receptors
have been often linked with prostate cancer specifically as the number of cells expressing calcitonin and calcitonin gene-related peptide
increases with prostate cancer progression with the bone being the most affected by the associated metastasis. Calcitonin peptide family
can promote prostate cancer cell growth via adenylyl cyclase and calcium/phospholipid pathways and can also increase invasion of cells
in vitro. Calcitonin peptide is not only upregulated in cancer cells but also promotes angiogenesis in hypoxic conditions and prevents
apoptosis whilst also suppressing the immune system thus aggravating the progression of the carcinogenesis and consequent metastasis.
Cell migration as a process in tumor metastasis is dependent and regulated by intracellular calcium levels induced by transient receptor
potential (TRP) channels. The channels have been found to promote the progression of prostate cancer towards a more aggressive
phenotype by stimulating migration and invasion in cells. Most calcitonin peptide family stimulates the TRP voltage 2 channel and
indirectly promotes tumor progression and metastasis. Many different neuropeptides including CGRP is expressed in the prostate gland
in both autonomic and sensory nerves and in neuroendocrine cells. Neuroendocrine cells are known to differentiate more frequently
in prostate cancer compared with many other cancer cells and correlates with tumor progression. It has long been known that CGRP
can increase invasion and migration capacity of prostate cancer cells by up to 30-40 % in vitro and that serum levels correlate with
prostate cancer progression in human patients. The role of CGRP receptors in promoting prostate cancer and its metastasis to the
bone is emerging clearly and rapidly too. The presence of CGRP and its secretory sensory and autonomic neurons in prostate cancer
models indicates that secretion of CGRP can also influence the bone microenvironment negatively in this regards. It is thus believed
that tumor-associated factors like CGRP can trigger the promotion of pathological sprouting of sensory neurons by increasing nerve
growth factor (NGF) expression more particularly within the bone microenvironment. Considering the significant roles played by
calcitonin peptide family and more specifically CGRP in aggravating the progression of prostate cancer and its metastasis to bone,
CGRP receptor antagonist either as non-peptide small molecules, monoclonal antibodies targeting the CGRP receptor or monoclonal
antibodies targeting the CGRP molecule may provide therapeutic interventions of prostate cancer and its associated bone metastasis
towards increasing the life expectancy of adult males particularly prostate cancer patients. It is very imperative to increase the debate,
discussion and research in this area to further expand the scope of information and existing knowledge towards new drug discoveries
and increased chemotherapeutic intervention against prostate cancer and its metastasis, hence this paper.
Lawrence Aka is a Professor of Veterinary Physiology in St. Matthew’s University, Cayman Islands, British West Indies. He had his DVM degree in 1996 from the University of Nigeria, Nsukka. In 2004 and 2010, he obtained his Master of Science and Doctor of Philosophy degrees respectively from the same University. He taught Veterinary Physiology at the University of Nigeria, from 1998-2016. He served as Head of the Department of Veterinary Physiology of same University until his appointment in St. Matthew’s University. He also taught Veterinary Physiology, as Visiting Professor, in various Universities including Usmanu Danfodiyo University Sokoto, Nigeria, from 2009-2016, University of Maiduguri, Nigeria, 2012-2014, University of Agriculture Markurdi, 2011-2013 e.t.c. He has supervised and examined several postgraduate projects in veterinary physiology. He has published several in reputable peer review journals. His areas of interest are 1. Hormonal regulation of digestive functions in ruminants and organic manipulation of rumen methane emission. 2. Impacts of environmental residues on animal reproduction. 3. Endocrine disruption and cancer biology. His current focus is on the antineoplastic properties of extracts from tropical plants. He is a recipient of several academic awards including the University of Nigeria faculty best student award at undergraduate and Doctoral levels. He has few research grants to his credit. He has authored several books including “Foundation of Veterinary Physiology” (1st edition, 2004, and 2nd edition, 2014) and others of general interest. He is a member of reputable professional organizations.