Colon cancer – new strategies of treatment
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Department of Internal Medicine, Angiology and Physical Medicine, Faculty in Medical Sciences in Zabrze, Medical Uniwersity of Silesia in Katowice
General Practitioner Practice, Hospital of the Ministry of the Interior and Administration in Katowice
Anna Międzybrodzka   

General Practitioner Practice, Hospital of the Ministry of the Interior and Administration in Katowice, Głowacki Street 10, 40-052 Katowice
Ann. Acad. Med. Siles. 2019;73:266–273
Colon cancer is one of the most frequent causes of death in the world. Despite the easily accessible diagnostic tools, the disease is still diagnosed at its advanced stage, when radical treatment is no longer possible and only palliative therapy can be provided. Cancer recurrence, which worsens the patient’s prognosis, is a separate problem. Currently, scientists are seeking modern, multidirectional treatment methods, which would enable the inhibition of neoplasia, elongation of patients’ lives and improvement in their quality. Immunotherapy and photodynamic therapy seem to be promising as they provide good results, also at advanced stages of cancer. Due to its cytotoxic and immunomodulating effect, photodynamic therapy exhibits an antineoplastic effect. Using monoclonal antibodies in the targeted therapy of colon cancer is a new, promising concept, which requires further studies.
Krzakowski M., Potemski P., Warzocha K., Wysocki P. Onkologia kliniczna. T. 2. Wyd. Via Medica. Gdańsk 2015.
Bartnik W., Wyrwicz L. Rak jelita grubego. W: Interna Szczeklika 2017. Red. P. Gajewki, A. Szczeklik. Wyd. Medycyna Praktyczna. Kraków 2017.
Vişovan I.I., Tanțău M., Pascu O., Ciobanu L., Tanțău A. The role of narrow band imaging in colorectal polyp detection. Bosn. J. Basic Med. Sci. 2017; 17(2): 152–158, doi: 10.17305/bjbms.2017.1686.
Backes Y., Moss A., Reitsma J.B., Siersema P.D., Moons L.M. Narrow Band Imaging, Magnifying Chromoendoscopy, and Gross Morphological Features for the Optical Diagnosis of T1 Colorectal Cancer and Deep Submucosal Invasion: A Systematic Review and Meta-Analysis. Am. J. Gastroenterol. 2017; 112(1): 54–64, doi: 10.1038/ajg.2016.403.
Har-Noy O., Katz L., Avni T., Battat R., Bessissow T., Yung D.E., Engel T., Koulaouzidis A., Eliakim R., Ben-Horin S., Kopylov U. Chromoendoscopy, Narrow-Band Imaging or White Light Endoscopy for Neoplasia Detection in Inflammatory Bowel Diseases. Dig. Dis. Sci. 2017; 62(11): 2982–2990, doi: 10.1007/s10620-017-4772-y.
Latos W., Sieroń A., Cieślar G., Kawczyk-Krupka A. The benefits of targeted endoscopic biopsy performed using the autofluorescence based diagnostic technique in 67 cases of diagnostically difficult gastrointestinal tumors. Photodiagnosis Photodyn. Ther. 2018; 23: 63–67, doi: 10.1016/j.pdpdt.2018.05.015.
Strzelczyk N., Kwiatek S., Latos W., Sieroń A., Stanek A. Does the Numerical Colour Value (NCV) correlate with preneoplastic and neoplastic colorectal lesions? Photodiagnosis Photodyn. Ther. 2018; 23: 353–361, doi: 10.1016/j.pdpdt.2018.07.012.
Bos J.L., Fearon E.R., Hamilton S.R., Verlaan-de Vries M., van Boom J.H., van der Eb A.J., Vogelstein B. Prevalence of ras gene mutations in human colorectal cancers. Nature 1987; 327(6120): 293–297.
Jass J.R. Colorectal cancer: a multipathway disease. Crit. Rev. Oncog. 2006; 12(3–4): 273–287.
Marszałek A., Szylberg L., Wiśniewska E., Janiczek M. Impact of COX-2, IL-1β, TNF-α, IL-4 and IL-10 on the process of carcinogenesis in the large bowel. Pol. J. Pathol. 2012; 63(4): 221–227.
Koller F.L., Hwang D.G., Dozier E.A., Fingleton B. Epithelial interleukin-4 receptor expression promotes colon tumor growth. Carcinogenesis 2010; 31(6): 1010–1017, doi: 10.1093/carcin/bgq044.
Nie W., Xue L., Sun G., Ning Y., Zhao X. Interleukin-6 -634C/G polymorphism is associated with lung cancer risk: a meta-analysis. Tumour Biol. 2014; 35(5): 4581–4587, doi: 10.1007/s13277-013-1602-5.
Esfandi F., Mohammadzadeh Ghobadloo S., Basati G. Interleukin-6 level in patients with colorectal cancer. Cancer Lett. 2006; 244(1): 76–78.
Galizia G., Orditura M., Romano C., Lieto E., Castellano P., Pelosio L., Imperatore V., Catalano G., Pignatelli C., De Vita F. Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin. Immunol. 2002; 102(2): 169–178.
Yeh K.Y., Li Y.Y., Hsieh L.L., Lu C.H., Chou W.C., Liaw C.C., Tang R.P., Liao S.K. Analysis of the Effect of Serum Interleukin-6 (IL-6) and Soluble IL-6 Receptor Levels on Survival of Patients with Colorectal Cancer. Jpn. J. Clin. Oncol. 2010; 40(6): 580–587, doi: 10.1093/jjco/hyq010.
Kwon K.A., Kim S.H., Oh S.Y., Lee S., Han J.Y., Kim K.H., Goh R.Y., Choi H.J., Park K.J., Roh M.S., Kim H.J., Kwon H.C., Lee J.H. Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and Creactive protein level in colorectal cancer. BMC Cancer 2010; 10: 203, doi: 10.1186/1471-2407-10-203.
Asfaha S., Dubeykovskiy A.N., Tomita H., Yang X., Stokes S., Shibata W., Friedman R.A., Ariyama H., Dubeykovskaya Z.A., Muthupalani S., Ericksen R. i wsp. Mice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis. Gastroenterology 2013; 144(1): 155–166, doi: 10.1053/j.gastro.2012.09.057.
Lurje G., Zhang W., Schultheis A.M., Yang D., Groshen S., Hendifar A.E., Husain H., Gordon M.A., Nagashima F., Chang H.M., Lenz H.J. Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer. Ann. Oncol. 2008; 19(10): 1734–1741, doi: 10.1093/annonc/mdn368.
Li A., Varney M.L., Singh R.K. Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials. Clin. Cancer Res. 2001; 7(10): 3298–3304.
Ning Y., Manegold P.C., Hong Y.K., Zhang W., Pohl A., Lurje G., Winder T., Yang D., LaBonte M.J., Wilson P.M., Ladner R.D., Lenz H.J. Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models. Int. J. Cancer 2011; 128(9): 2038–2049, doi: 10.1002/ijc.25562.
Rubie C., Kollmar O., Frick V.O., Wagner M., Brittner B., Gräber S., Schilling M.K. Differential CXC receptor expression in colorectal carcinomas. Scand. J. Immunol. 2008; 68(6): 635–644, doi: 10.1111/j.1365-3083.2008.02163.x.
Ning Y., Lenz H.J. Targeting IL-8 in colorectal cancer. Expert Opin. Ther. Targets 2012; 16(5): 491–497, doi: 10.1517/14728222.2012.677440.
Huang Y., Cao Y., Zhang S., Gao F. Association between low expression levels of interleukin-9 and colon cancer progression. Exp. Ther. Med. 2015; 10(3): 942–946.
O’Hara R.J., Greenman J., MacDonald A.W., Gaskell K.M., Topping K.P., Duthie G.S., Kerin M.J., Lee P.W., Monson J.R. Advanced colorectal cancer is associated with impaired interleukin 12 and enhanced interleukin 10 production. Clin. Cancer Res. 1998; 4(8): 1943–1948.
Stanilov N., Miteva L., Deliysky T., Jovchev J., Stanilova S. Advanced colorectal cancer is associated with enhanced IL-23 and IL-10 serum levels. Lab. Med. 2010; 41(3): 159–163.
Putoczki T.L., Thiem S., Loving A., Busuttil R.A., Wilson N.J., Ziegler P.K., Nguyen P.M., Preaudet A., Farid R., Edwards K.M., Boglev Y. i wsp. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell. 2013; 24(2): 257–271, doi: 10.1016/j.ccr.2013.06.017.
Mertz K.D., Mager L.F., Wasmer M.H., Thiesler T., Koelzer V.H., Ruzzante G., Joller S., Murdoch J.R., Brümmendorf T., Genitsch V., Lugli A. i wsp. The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice. Oncoimmunology 2015; 5(1): e1062966.
Cui G., Qi H., Gundersen M.D., Yang H., Christiansen I., Sørbye S.W., Goll R., Florholmen J. Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer. Cancer Immunol. Immunother. 2015; 64(2): 181–190, doi: 10.1007/s00262-014-1624-x.
Maywald R.L., Doerner S.K., Pastorelli L., De Salvo C., Benton S.M., Dawson E.P., Lanza D.G., Berger N.A., Markowitz S.D., Lenz H.J., Nadeau J.H. i wsp. IL-33 activates tumor stroma to promote intestinal polyposis. Proc. Natl. Acad. Sci. USA 2015; 112(19): E2487–2496, doi: 10.1073/pnas.1422445112.
Eppenberger M., Zlobec I., Baumhoer D., Terracciano L., Lugli A. Role of the VEGF ligand to receptor ratio in the progression of mismatch repairproficient colorectal cancer. BMC Cancer 2010; 10: 93, doi: 10.1186/1471-2407-10-93.
Friedl P., Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat. Rev. Cancer 2003; 3(5): 362–374.
Kwiatkowski P., Godlewski J., Śliwińska-Jewsiewicka A., Kmieć Z. Cząsteczki adhezyjne w procesie nowotworzenia i przerzutowania. Pol. Ann. Med. 2009; 16(1): 128–137.
Scheller J., Ohnesorge N., Rose-John S. Interleukin-6 trans-signalling in chronic inflammation and cancer. Scand. J. Immunol. 2006; 63(5): 321–329.
Keller E.T., Wanagat J., Ershler W.B. Molecular and cellular biology of interleukin-6 and its receptor. Front. Biosci. 1996; 1: d340–357.
Shih J.Y., Yuan A., Chen J.J.W., Yang P.C. Tumor-Associated Macrophage: Its Role in Cancer Invasion and Metastasis. J. Cancer Mol. 2006; 2(3): 101–106.
Jackson S.E., Chester J.D. Personalised cancer medicine. Int. J. Cancer 2015; 137(2): 262–266, doi: 10.1002/ijc.28940.
Tu S.M., Bilen M.A., Tannir N.M. Personalised cancer care: promises and challenges of targeted therapy. J. R. Soc. Med. 2016; 109(3): 98–105, doi: 1177/0141076816631154.
Brittain H.K., Scott R., Thomas E. The rise of the genome and personalised medicine. Clin. Med. (Lond.) 2017; 17(6): 545–551, doi: 10.7861/clinmedicine.17-6-545.
Sticz T., Molnár A., Dankó T., Hujber Z., Petővári G., Nagy N., Végső G., Kopper L., Sebestyén A. The Effects of Different mTOR Inhibitors in EGFR Inhibitor Resistant Colon Carcinoma Cells. Pathol. Oncol. Res. 2018; doi: 10.1007/s12253-018-0434-4.
Li B., Gao S., Wei F., Bellail AC, Hao C, Liu T. Simultaneous targeting of EGFR and mTOR inhibits the growth of colorectal carcinoma cells. Oncol. Rep. 2012; 28(1): 15–20, doi: 10.3892/or.2012.1786.
Herzig D.O., Tsikitis V.L. Molecular markers for colon diagnosis, prognosis and targeted therapy. J. Surg. Oncol. 2015; 111(1): 96–102, doi: 10.1002/jso.23806.
Kowalik A. Diagnostyka w medycynie personalizowanej. W: Medycyna personalizowana. Mity, fakty, rekomendacje. Red. A. Fronczak. Wyd. Plexus s.c. Łódź 2016, s. 66–68.
Brown S.B., Brown E.A., Walker I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 2004; 5(8): 497–508.
Sieroń A., Kwiatek S. Twenty years of experience with PDD and PDT in Poland – Review. Photodiagnosis Photodyn. Ther. 2009; 6(2): 73–78, doi: 10.1016/j.pdpdt.2009.07.003.
Kousis P.C., Henderson B.W., Maier P.G., Gollnick S.O. Photodynamic therapy enhancement of antitumor immunity is regulated by neutrophils. Cancer Res. 2007; 67(21): 10501–10510.
Kawczyk-Krupka A., Sieroń-Stołtny K., Latos W., Czuba Z.P., Kwiatek B., Potempa M., Wasilewska K., Król W., Stanek A. ALA-induced photodynamic effect on vitality, apoptosis, and secretion of vascular endothelial growth factor (VEGF) by colon cancer cells in normoxic environment in vitro. Photodiagnosis Photodyn. Ther. 2016; 13: 308–315, doi: 10.1016/j.pdpdt.2015.09.003.
Herrera-Ornelas L., Petrelli N.J., Mittelman A., Dougherty T.J., Boyle D.G. Photodynamic therapy in patients with colorectal cancer. Cancer 1986; 57(3): 677–684.
Mlkvy P., Messmann H., Regula J., Conio M., Pauer M., Millson C.E., MacRobert A.J., Bown S.G. Photodynamic therapy for gastrointestinal tumors using three photosensitizers–ALA induced PPIX, Photofrin and MTHPC. A pilot study. Neoplasma 1998; 45(3): 157–161.
Mlkvy P., Messmann H., Debinski H., Regula J., Conio M., MacRobert A., Spigelman A., Phillips R., Bown S.G. Photodynamic therapy for polyps in familial adenomatous polyposis–a pilot study. Eur. J. Cancer 1995; 31A(7–8): 1160–1165.
Regula J., MacRobert A.J., Gorchein A., Buonaccorsi G.A., Thorpe S.M., Spencer G.M., Hatfield A.R., Bown S.G. Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5-aminolaevulinic acid induced protoporphyrin IX–a pilot study. Gut 1995; 36(1): 67–75.
Sun B.O., Li W., Liu N. Curative effect of the recent photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer. Oncol. Lett. 2016; 11(3): 2071–2074.
He J., Yang L., Yi W., Fan W., Wen Y., Miao X., Xiong L. Combination of Fluorescence-Guided Surgery With Photodynamic Therapy for the Treatment of Cancer. Mol. Imaging 2017; 16: 1536012117722911, doi: 10.1177/1536012117722911.
Kleinovink J.W., van Driel P.B., Snoeks T.J., Prokopi N., Fransen M.F., Cruz L.J., Mezzanotte L., Chan A., Löwik C.W., Ossendorp F. Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors. Clin. Cancer Res. 2016; 22(6): 1459–1468, doi: 10.1158/1078-0432.CCR-15-0515.
Kaleta-Richter M., Kawczyk-Krupka A., Aebisher D., Bartusik-Aebisher D., Czuba Z., Cieślar G. The capability and potential of new forms of personalized colon cancer treatment – immunotherapy and photodynamic therapy. Photodiagnosis Photodyn. Ther. 2019; 25: 253–258, doi: 10.1016/j.pdpdt.2019.01.004.
Peng C.L., Lin H.C., Chiang W.L., Shih Y.H., Chiang P.F., Luo T.Y., Cheng C.C., Shieh M.J. Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer. Photodiagnosis Photodyn. Ther. 2018; 23: 111–118, doi: 10.1016/j.pdpdt.2018.06.008.