Rihin Chavda

Introduction: It is well established that inflammation is strongly associated with colorectal carcinogenesis. Pathology of acute and chronic inflammation contribute to genomic damage and promotion of cancer ⁽⁷⁾. Fc therapy has been exploited in many forms of cancers to deliver immunoconjugates that deliver the toxin or radioisotope readily. The delivery of anti-inflammation Fc therapy can be used to hinder growth factors, angiogenesis, and inflammatory mediators. These therapy methods can lessen the progression of colorectal carcinogenesis ^(1,3-5). Methods: Angiogenesis is one of the key processes of inflammation, leading to increased blood supply to tumor cells. When increased blood supply occurs, platelet interaction with cancer cells increases metastasis. One study measured VEGF concentrations released by platelets upon interaction with tumor cells (MCF-7) with and without administration of anticoagulants ⁽⁵⁾. Another study measured administration of an anti-VEGF drug, bevacizumab, and checked tumor size via ultrasound ⁽⁸⁾. Another study administered Revacept to HT29 CRC cells co-cultured with platelets and checked COX-2 levels in cell lysates ⁽²⁾. Results: As expected, VEGF concentrations released were higher among platelets allowed to interact with cancer cells without anti-coagulants present ⁽⁵⁾. In a study that measured tumor size via ultrasound after administration of anti-VEGF drug bevacizumab further proved the importance of angiogenesis in carcinogenesis ⁽⁸⁾. With Bevacizumab administration, tumor size had decreased and progression free survival had increased. Other physiological changes occurring concurrently with angiogenesis include increased platelets interaction with cancer cells. Platelet’s GPVI receptors interact with cancer cells, causing increased expression of COX-2⁽²⁾. Conclusion: New therapies that utilize Fc receptors and deliver immunocongjugated molecules to CRC cells can provide new avenues of targeted therapy. Several therapies are already in use, Bevacizumab is a recombinant antibody that binds and blocks VEGF-A, blocking angiogenesis ⁽¹⁾. Revacept is a GPVI-Fc fusion protein that interrupts platelet interaction and activation of malignancy in CRC ^(3-5). Another novel area of research includes GFI1, which is a transcription factor that downregulates inflammatory mediators. In tumor cells, this factor is not expressed heavily. By artificially delivering this protein, there is potential to decrease inflammatory benefit in CRC carcinogenesis ⁽⁴⁾. Fc receptor targeting of inflammation pathophysiology and its mediators can be greatly appreciated in decreasing CRC progression and severity.

1. Caulet M, Lecomte T, Bouché O, et al. Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients.Clinical Pharmacokinetics. 2016;55(11):1381-1394. doi:10.1007/s40262-016-0406-3.
2. Dovizio M, Maier TJ, Alberti S, et al. Pharmacological Inhibition of Platelet-Tumor Cell Cross-Talk Prevents Platelet-Induced Overexpression of Cyclooxygenase-2 in HT29 Human Colon Carcinoma Cells.Molecular Pharmacology. 2013;84⁽¹⁾:25-40. doi:10.1124/mol.113.084988.
3. Ungerer M, Li Z, Baumgartner C, et al. The GPVI – Fc Fusion Protein Revacept Reduces Thrombus Formation and Improves Vascular Dysfunction in Atherosclerosis without Any Impact on Bleeding Times. Xiao Q, ed.PLoS ONE. 2013;8(8):e71193. doi:10.1371/journal.pone.0071193.
4. Xing W, Xiao Y, Lu X, et al. GFI1 downregulation promotes inflammation-linked metastasis of colorectal cancer.Cell Death and Differentiation. July 2017. doi:10.1038/cdd.2017.50.
5. Battinelli EM, Markens BA, Kulenthirarajan RA, Machlus KR, Flaumenhaft R, Italiano JE. Anticoagulation inhibits tumor cell–mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response.Blood. 2014;123⁽¹⁾:101-112. doi:10.1182/blood-2013-02-485011.
6. Dovizio M, Sacco A, Patrignani P. Curbing tumorigenesis and malignant progression through the pharmacological control of the wound healing process.Vascular Pharmacology. 2017;89:1-11. doi:10.1016/j.vph.2017.01.003.
7. Kidane D, Chae WJ, Czochor J, et al. Interplay between DNA repair and inflammation, and the link to cancer.Critical reviews in biochemistry and molecular biology. 2014;49⁽²⁾:116-139. doi:10.3109/10409238.2013.875514.
8. Wu Z, Yang X, Chen L, et al. Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis. Li. J, ed. Medicine. 2017;96(20):e6731. doi:10.1097/MD.0000000000006731.