Effect Of Vitamin D In Metastasis Of Colorectal Cancer: A Study Revealing The Pathophysiological Illustration Of Bio-Molecular Interactions

Abstract

Globally, ~1,800,000 new cases are diagnosed every year and now accounts for approximately 10% of cancer-related mortality in western countries and the number of new cases may increase to nearly 2.5 million in 2035. In the pathobiology of CRC included various different factors and bio-molecules aggravation such as a immunohistochemistry indicated increased TMPRSS13 protein levels,Chemokine ligand 20 (CCL20) mediated abnormally expression of Engrailed-2 (EN2),persistent inflammation, hypercoagulation and IL-6/JAK2/STAT3 signaling, which activated PI3K/AKT signaling,Notchsignalling, Hedgehog pathway,TGF-β (transforming growth factor-β)/SMAD,and RAS/rapidly accelerated fibrosarcoma (RAF).However, great progress has been achieved in multimodality therapy of CRC, the prognosis of late-stage CRC is still unsatisfactory due to distant metastasis and relapse. Although, targeted therapies have been successful in the treatment of some types of cancers, such as breast cancer, they have limited efficacy in adjuvant treatment of colorectal cancer (i.e., cetuximab, panitumumab, bevacizumab, ramucirumab, zivaflibercept, and regorafenib) and add relatively small survival benefits for those with advanced disease. From previous years Wnt/β-catenin canonical signalling pathway coming into picture of CRC.According to the Cancer Genome Atlas more than 94% of cases of colorectal cancer have mutations in one or more Wnt/β-catenin signalling pathway components, suggesting that Wnt/β-catenin canonical signallingmechanism are important hallmark of both the early stages and the late stages for cell proliferation and migration and tumorigenesis in CRC. Thus, our primary aim in study to investigate different target sites of Wnt/β-cateninsignalling and up regulatory axis that involve in progression of CRC. And secondary aim to identify the role of vitamin D in influencing site of the targeted Wnt/β-catenin pathway.