{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:48:18Z","timestamp":1792090098665,"version":"4.4.0"},"reference-count":185,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T00:00:00Z","timestamp":1699747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Cancer Society Diversity in Cancer Research Institutional Development","award":["DICRIDG-21-074-01-DICRIDG"],"award-info":[{"award-number":["DICRIDG-21-074-01-DICRIDG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university\u2019s online library. The keywords were \u201cColorectal Cancer\u201d AND \u201cdisease process\u201d OR \u201cdisease mechanisms\u201d OR \u201cCurrent Treatment\u201d OR \u201cProspects\u201d. Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews\/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low\u2013medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7\u201310 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin\u00ae), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux\u00ae) and panitumumab (Verbitix\u00ae). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.<\/jats:p>","DOI":"10.3390\/pharmaceutics15112620","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:10:43Z","timestamp":1699841443000},"page":"2620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":128,"title":["Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives"],"prefix":"10.3390","volume":"15","author":[{"given":"Amusa S.","family":"Adebayo","sequence":"first","affiliation":[{"name":"College of Pharmacy, Howard University, 2400 6th St NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kafilat","family":"Agbaje","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Howard University, 2400 6th St NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon K.","family":"Adesina","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Howard University, 2400 6th St NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwabukunmi","family":"Olajubutu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Howard University, 2400 6th St NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040","volume":"14","author":"Xi","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhang, C., Wang, Q., Wu, K., Sun, Z., Tang, Z., and Zhang, B. (2023, October 23). Global, Regional, and National Burden of Colorectal Cancer and Attributable Risk Factors, from 1990 to 2019: Updated Results from the Global Burden of Disease Study 2019. Available online: https:\/\/www.researchsquare.com\/article\/rs-1478628\/v1.","DOI":"10.21203\/rs.3.rs-1478628\/v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"g2467","DOI":"10.1136\/bmj.g2467","article-title":"Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: Systematic review and meta-analysis of randomized controlled trials and observational studies","volume":"348","author":"Brenner","year":"2014","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1136\/gutjnl-2014-309086","article-title":"Colorectal cancer screening: A global overview of existing programmes","volume":"64","author":"Schreuders","year":"2015","journal-title":"Gut"},{"key":"ref_6","unstructured":"World Health Organization (2023, August 17). WHO Report on Cancer: Setting Priorities, Investing Wisely and Providing Care for All. World Health Organization, Available online: https:\/\/www.who.int\/publications-detail-redirect\/9789240001299."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3322\/caac.21772","article-title":"Colorectal cancer statistics 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_8","unstructured":"American Cancer Society (ACS) (2022). Cancer Facts & Figures, American Cancer Society. Available online: https:\/\/www.cancer.org\/research\/cancer-facts-statistics\/all-cancer-facts-figures\/cancer-facts-figures-2022.html."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1111\/j.1365-2036.2012.05119.x","article-title":"Risk of colorectal adenomas and advanced neoplasia in Hispanic, black and white patients undergoing screening colonoscopy","volume":"35","author":"Lebwohl","year":"2012","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s00384-020-03585-z","article-title":"Social determinants of colorectal cancer risk, stage, and survival: A systematic review","volume":"35","author":"Coughlin","year":"2020","journal-title":"Int. J. Color. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Engin, O., Kilinc, G., and Salimoglu, S. (2020). Trends, risk factors, and preventions in colorectal cancer. Colon. Polyps Color. Cancer, 213\u2013233.","DOI":"10.1007\/978-3-030-57273-0_10"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1038\/onc.2015.522","article-title":"Adenomatous polyposis coli (APC) regulates MIR17-92 cluster through \u03b2-catenin pathway in colorectal cancer","volume":"35","author":"Li","year":"2016","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"djw332","DOI":"10.1093\/jnci\/djw332","article-title":"Multiple roles of APC and its therapeutic implications in colorectal cancer","volume":"109","author":"Zhang","year":"2017","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhou, J.J. (2014). MicroRNA regulation network in colorectal cancer metastasis. World J. Biol. Chem., 5.","DOI":"10.4331\/wjbc.v5.i3.301"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"l803","DOI":"10.1136\/bmj.l803","article-title":"Familial colorectal cancer risk in half siblings and siblings: Nationwide cohort study","volume":"364","author":"Tian","year":"2019","journal-title":"BMJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41575-019-0189-8","article-title":"Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies","volume":"16","author":"Keum","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Karuniawati, H., Jairoun, A.A., Urbi, Z., Ooi, D.J., John, A., and Hadi, M.A. (2022). Colorectal cancer: A review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers, 14.","DOI":"10.3390\/cancers14071732"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1158\/1940-6207.CAPR-16-0124","article-title":"Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management Colorectal Cancer in Inflammatory Bowel Disease","volume":"9","author":"Dulai","year":"2016","journal-title":"Cancer Prev. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"509348","DOI":"10.1155\/2012\/509348","article-title":"Genetic and epigenetic events generate multiple pathways in colorectal cancer progression","volume":"2012","author":"Pancione","year":"2012","journal-title":"Pathol. Res. Int."},{"key":"ref_20","first-page":"43","article-title":"New intracellular and molecular aspects in pathophysiology of colorectal cancer","volume":"4","author":"Ziapour","year":"2011","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.currproblcancer.2018.06.010","article-title":"The impact of microsatellite stability status in colorectal cancer","volume":"42","author":"Gupta","year":"2018","journal-title":"Curr. Probl. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1158\/0008-5472.CAN-18-3235","article-title":"Chromosomal instability in tumor initiation and development","volume":"79","author":"Bach","year":"2019","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.2217\/nnm-2016-0194","article-title":"Targeted nanoparticles for colorectal cancer","volume":"11","author":"Cisterna","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1046\/j.1432-1327.2001.02073.x","article-title":"Receptor mediated uptake of peptides that bind the human transferrin receptor","volume":"268","author":"Lee","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"541","DOI":"10.18433\/J3B303","article-title":"Transferrin receptor mediated brain uptake during ischemia and reperfusion","volume":"16","author":"Hao","year":"2013","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_26","unstructured":"Abegg, D., Gasparini, G., Hoch, D.G., and Shuster, A. (2023, August 17). Strained Cyclic Disulfides Enable Cellular Uptake by Reacting with the Transferrin Receptor. Available online: https:\/\/pubs.acs.org\/doi\/suppl\/10.1021\/jacs.6b09643\/suppl_file\/ja6b09643_si_001.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rapoport, S.M. (2020). The Reticulocyte, CRC Press.","DOI":"10.1201\/9780429281174"},{"key":"ref_28","first-page":"A32","article-title":"IDDF2022-ABS-0024 Transferrin Receptor-Mediated Iron Uptake Is Essential for Colon Tumorigenesis","volume":"71","author":"Xue","year":"2022","journal-title":"Basic. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1002\/ijc.34407","article-title":"Association of screening status, polygenic risk score and environmental risk factors with colorectal cancer incidence and mortality risks","volume":"152","author":"Ren","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.cgh.2022.08.046","article-title":"Initial impact of national CRC screening on incidence and advanced colorectal cancer","volume":"21","author":"Krul","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1055\/s-0041-1736343","article-title":"Long-Term Survivors of Metastatic Colorectal Cancer: A Tertiary Care Centre Experience","volume":"10","author":"Sharma","year":"2021","journal-title":"South. Asian J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s10549-020-06083-6","article-title":"Global, regional, national burden of breast cancer in 185 countries: Evidence from Globocan 2018","volume":"187","author":"Sharma","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1056\/NEJMoa2208375","article-title":"Effect of colonoscopy screening on risks of colorectal cancer and related death","volume":"387","author":"Bretthauer","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Diedrich, L., Brinkmann, M., Dreier, M., Rossol, S., Schramm, W., and Krauth, C. (2023). Is there a place for sigmoidoscopy in colorectal cancer screening? A systematic review and critical appraisal of cost-effectiveness models. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0290353"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"JC19","DOI":"10.7326\/J22-0113","article-title":"In adults, sigmoidoscopy screening invitation reduced CRC incidence and related mortality at 15 y","volume":"176","author":"Imperiale","year":"2023","journal-title":"Ann. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Erdogan, A., and Lee, Y.Y. (2020). Colon and pelvic floor anatomy and physiology. Clin. Basic. Neurogastroenterol. Motil., 113\u2013126.","DOI":"10.1016\/B978-0-12-813037-7.00008-X"},{"key":"ref_37","unstructured":"Bharucha, A.E., and Camilleri, M. (2019). Shackelford\u2019s Surgery of the Alimentary Tract, Elsevier."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/ijc.10635","article-title":"Are there two sides to colorectal cancer?","volume":"101","author":"Iacopetta","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/jso.20156","article-title":"Two colons-two cancers: Paradigm shift and clinical implications","volume":"88","author":"Gervaz","year":"2004","journal-title":"J. Surg. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hemminki, K., Santi, I., Weires, M., Thomsen, H., Sundquist, J., and Bermejo, J.L. (2010). Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-688"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/cncr.29129","article-title":"Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease?","volume":"12","author":"Price","year":"2015","journal-title":"Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejca.2017.07.016","article-title":"Understanding the role of primary tumour localization in colorectal cancer treatment and outcomes","volume":"84","author":"Stintzing","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3393\/ac.2017.33.6.210","article-title":"Is the location of the tumor another prognostic factor for patients with colon cancer?","volume":"33","author":"Jung","year":"2017","journal-title":"Ann. Coloproctol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cll.2004.12.010","article-title":"From colonic polyps to colon cancer: Pathophysiology, clinical presentation, and diagnosis","volume":"25","author":"Cappell","year":"2005","journal-title":"Clin. Lab. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"dju427","DOI":"10.1093\/jnci\/dju427","article-title":"Primary tumor location as a prognostic factor in metastatic colorectal cancer","volume":"107","author":"Loupakis","year":"2015","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ejso.2014.11.001","article-title":"Is right-sided colon cancer different to left-sided colorectal cancer? \u2013a systematic review","volume":"41","author":"Lee","year":"2015","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100633","DOI":"10.1016\/j.esmoop.2022.100633","article-title":"Pooled safety analysis from phase III studies of trifluridine\/tipiracil in patients with metastatic gastric or gastroesophageal junction cancer and metastatic colorectal cancer","volume":"7","author":"Hochster","year":"2022","journal-title":"ESMO Open"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.3394","article-title":"Microenvironmental regulation of tumor progression and metastasis","volume":"19","author":"Quail","year":"2013","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbcan.2016.11.001","article-title":"Colantuoni, Friend or foe?: The tumor microenvironment dilemma in colorectal cancer","volume":"1867","author":"Colangelo","year":"2017","journal-title":"Biochim. Et. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_51","first-page":"482","article-title":"Cancer associated fibroblasts: The dark side of the coin","volume":"1","author":"Cirri","year":"2011","journal-title":"Am. J. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/onc.2012.536","article-title":"Interaction with colon cancer cells hyperactivates TGF-\u03b2 signaling in cancer-associated fibroblasts","volume":"33","author":"Paauwe","year":"2014","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.semcancer.2014.02.006","article-title":"Prognostic relevance of cancer-associated fibroblasts in human cancer","volume":"Volume 25","author":"Paulsson","year":"2014","journal-title":"Seminars in Cancer Biology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/S0140-6736(83)92719-8","article-title":"Unidentified curved bacilli on gastric epithelium in active chronic gastritis","volume":"321","author":"Robinwarren","year":"1983","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.3748\/wjg.v23.i9.1521","article-title":"Host pathogen interactions in helicobacter pylori related gastric cancer","volume":"23","author":"Chmiela","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijmm.2004.06.014","article-title":"Helicobacter pylori: Recombination, population structure and human migrations","volume":"294","author":"Suerbauma","year":"2004","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00384-008-0479-z","article-title":"Meta-analysis of different test indicators: Helicobacter pylori infection and the risk of colorectal cancer","volume":"23","author":"Zhao","year":"2008","journal-title":"Int. J. Color. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/MD.0000000000021832","article-title":"Association between Helicobacter pylori infection and the risk of colorectal cancer: A systematic review and meta-analysis","volume":"99","author":"Zuo","year":"2020","journal-title":"Medicine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/aje\/kwr331","article-title":"Helicobacter pylori infection and colorectal cancer risk: Evidence from a large population-based case-control study in Germany","volume":"175","author":"Zhang","year":"2012","journal-title":"Am. J. Epidemiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez de Larrea-Baz, N., Michel, A., Romero, B., P\u00e9rez-G\u00f3mez, B., Moreno, V., Mart\u00edn, V., Dierssen-Sotos, T., Jim\u00e9nez-Mole\u00f3n, J.J., Castilla, J., and Tard\u00f3n, A. (2017). Helicobacter pylori Antibody Reactivities and Colorectal Cancer Risk in a Case-control Study in Spain. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00888"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1053\/j.gastro.2018.09.054","article-title":"Serologic response to Helicobacter pylori proteins associated with risk of colorectal cancer among diverse populations in the United States","volume":"156","author":"Butt","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11654","DOI":"10.3748\/wjg.v21.i41.11654","article-title":"Role of Helicobacter pylori infection in gastric carcinogenesis: Current knowledge and future directions","volume":"21","author":"Alempijevic","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_63","first-page":"50","article-title":"Molecular anatomy and pathogenic actions of helicobacter pylori CagA that underpin gastric carcinogenesis","volume":"17","author":"Knight","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"ref_64","unstructured":"World Health Organization (2023, August 17). WHO Publishes List of Bacteria for which New Antibiotics Are Urgently Needed. World Health Organization, Available online: https:\/\/www.who.int\/news\/item\/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Srisuphanunt, M., Wilairatana, P., Kooltheat, N., Duangchan, T., Katzenmeier, G., and Rose, J.B. (2023). Molecular mechanisms of antibiotic resistance and novel treatment strategies for helicobacter pylori infections. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8030163"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cardos, A.I., Maghiar, A., Zaha, D.C., Pop, O., Fritea, L., Miere, F., and Cavalu, S. (2022). Evolution of diagnostic methods for helicobacter pylori infections: From traditional tests to high technology, advanced sensitivity and discrimination tools. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020508"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00262-021-03013-3","article-title":"Chemotherapy: A double-edged sword in cancer treatment","volume":"71","author":"Behranvand","year":"2022","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10147-017-1101-6","article-title":"Japanese Society for Cancer of the Colon and Rectum Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines for the treatment of colorectal cancer","volume":"23","author":"Watanabe","year":"2018","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/bmb\/64.1.101","article-title":"Surgery for colorectal cancer","volume":"64","author":"Dorudi","year":"2002","journal-title":"Br. Med. Bull."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1097\/DCR.0000000000002323","article-title":"The American Society of Colon and Rectal Surgeons clinical practice guidelines for the management of colon cancer","volume":"65","author":"Vogel","year":"2022","journal-title":"Dis. Colon. Rectum"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.amsu.2020.04.024","article-title":"Surgical complications in colorectal cancer patients","volume":"55","author":"Pak","year":"2020","journal-title":"Ann. Med. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/ags3.12401","article-title":"Robotic surgery for colorectal cancer","volume":"4","year":"2020","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_73","first-page":"S9","article-title":"Cancer cryotherapy: Evolution and biology","volume":"6","author":"Theodorescu","year":"2004","journal-title":"Rev. Urol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cryobiol.2023.05.004","article-title":"Suitable T stage for cryosurgery to spare the anus in patients with low rectal cancer","volume":"111","author":"Jiang","year":"2023","journal-title":"Cryobiology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.ejso.2007.01.003","article-title":"Cryosurgery for resectable and unresectable hepatic metastases from colorectal cancer","volume":"33","author":"Bageacu","year":"2007","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1126\/science.aaa6204","article-title":"T cell exclusion, immune privilege, and the tumor microenvironment","volume":"348","author":"Joyce","year":"2015","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fimmu.2019.00193","article-title":"Role of radiation therapy in modulation of the tumor stroma and microenvironment","volume":"10","author":"Menon","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13014-016-0752-1","article-title":"Intraoperative radiation therapy for colon and rectal cancers: A clinical review","volume":"12","author":"Haddock","year":"2017","journal-title":"Radiat. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13014-020-1458-y","article-title":"Intraoperative radiotherapy as an immediate adjuvant treatment of rectal cancer due to limited access to external-beam radiotherapy","volume":"15","author":"Potemin","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1089\/jpm.2010.0124","article-title":"Surviving chemotherapy for colon cancer and living with the consequences","volume":"13","author":"Tofthagen","year":"2010","journal-title":"J. Palliat. Med."},{"key":"ref_81","first-page":"162","article-title":"Adjuvant chemotherapy for colon cancer in the elderly: Moving from evidence to practice","volume":"23","author":"Ades","year":"2009","journal-title":"Oncology"},{"key":"ref_82","first-page":"134","article-title":"Principles of cancer treatment by chemotherapy","volume":"36","author":"Dickens","year":"2018","journal-title":"Surgery"},{"key":"ref_83","first-page":"173","article-title":"Principles of cancer treatment by chemotherapy","volume":"27","author":"Bhosle","year":"2009","journal-title":"Surgery"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-fluorouracil: Mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.3816\/CCC.2005.s.007","article-title":"Benefits and drawbacks of the use of oral fluoropyrimidines as single-agent therapy in advanced colorectal cancer","volume":"5","author":"Cassidy","year":"2005","journal-title":"Clin. Color. Cancer"},{"key":"ref_86","first-page":"5769","article-title":"Methacrylic-based nanogels for the pH-sensitive delivery of 5-fluorouracil in the colon","volume":"7","author":"Ashwanikumar","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_87","first-page":"1112","article-title":"Formulation and evaluation porous microspheres of 5-fluorouracil for colon targeting","volume":"2","author":"Dhawale","year":"2010","journal-title":"Int. J. Pharm. Tech. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"104398","DOI":"10.1016\/j.phrs.2019.104398","article-title":"Irinotecan: 25 years of cancer treatment","volume":"148","author":"Bailly","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/jcph.1275","article-title":"Pharmacometabolomics reveals irinotecan mechanism of action in cancer patients","volume":"59","author":"Bao","year":"2019","journal-title":"J. Clin. Pharmacol."},{"key":"ref_90","unstructured":"Reyhanoglu, G., and Smith, T. (2023). Irinotecan in StatPearls, StatPearls Publishing."},{"key":"ref_91","first-page":"86","article-title":"Fatty liver and drugs: The two sides of the same coin","volume":"21","author":"Miele","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1111\/cas.15377","article-title":"Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs","volume":"113","author":"Milano","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_93","first-page":"1803","article-title":"Treatment of advanced colorectal and gastric adenocarcinomas with 5-FU combined with high-dose folinic acid: A pilot study","volume":"66","author":"Machover","year":"1982","journal-title":"Cancer Treat. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1200\/JCO.2004.03.104","article-title":"Meta-Analysis Group in Cancer Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: An updated meta-analysis","volume":"22","author":"Thirion","year":"2004","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2217\/nnm-2021-0423","article-title":"pH-sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer","volume":"17","author":"Ibrahim","year":"2022","journal-title":"Nanomedicine"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.ejca.2004.02.014","article-title":"Monoclonal antibodies in the treatment of colorectal cancer","volume":"40","author":"Veronese","year":"2004","journal-title":"Eur. J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.1200\/JCO.2005.02.194","article-title":"Targeting signal transduction pathways in colorectal cancer\u2014More than skin deep","volume":"23","author":"Cohen","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1200\/JCO.2002.10.088","article-title":"Vascular permeability factor\/vascular endothelial growth factor: A critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy","volume":"20","author":"Dvorak","year":"2002","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1093\/jnci\/95.12.851","article-title":"Developing inhibitors of the epidermal growth factor receptor for cancer treatment","volume":"95","author":"Hidalgo","year":"2003","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"11793","DOI":"10.3748\/wjg.v21.i41.11793","article-title":"Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update","volume":"21","author":"Aprile","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.2174\/092986711797287584","article-title":"Development of 5-fluorouracil derivatives as anticancer agents","volume":"18","author":"Pan","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5158","DOI":"10.3748\/wjg.v21.i17.5158","article-title":"Chemotherapy for colorectal cancer in the elderly","volume":"21","author":"Kim","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1200\/JCO.20.02447","article-title":"Primary tumor resection plus chemotherapy versus chemotherapy alone for colorectal cancer patients with asymptomatic, synchronous unresectable metastases (JCOG1007; ipacs): A randomized clinical trial","volume":"39","author":"Kanemitsu","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1080\/14756366.2019.1655406","article-title":"Design and application of Oral Colon Administration System","volume":"34","author":"Cheng","year":"2019","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jconrel.2021.12.030","article-title":"Evolution of drug delivery systems: From 1950 to 2020 and beyond","volume":"342","author":"Park","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/cbdd.13125","article-title":"Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides","volume":"91","author":"Williams","year":"2017","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41467-022-27995-5","article-title":"Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction","volume":"13","author":"Islam","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"119912","DOI":"10.1016\/j.ijpharm.2020.119912","article-title":"Advances in drug delivery systems: Work in progress still needed?","volume":"590","author":"Laffleur","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1002\/jcp.26041","article-title":"Targeting the tumor microenvironment as a potential therapeutic approach in colorectal cancer: Rational and progress","volume":"233","author":"Bahrami","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_110","first-page":"37","article-title":"Colon targeted drug delivery system: A review system","volume":"1","author":"Patel","year":"2011","journal-title":"J. Pharm. Sci. Biosci. Res."},{"key":"ref_111","first-page":"157","article-title":"Report on pharmaceutical approaches to colon targeted drug delivery systems","volume":"3","author":"Kumar","year":"2010","journal-title":"J. Pharm. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1208\/s12249-015-0350-9","article-title":"Colon-targeted oral drug delivery systems: Design trends and approaches","volume":"16","author":"Amidon","year":"2015","journal-title":"AAPS Pharm. SciTech"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1517\/17425247.2013.821978","article-title":"pH-and ion-sensitive polymers for drug delivery","volume":"10","author":"Yoshida","year":"2013","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_114","first-page":"1","article-title":"Pectin-HPMC E15LV vs. pH sensitive polymer coating films for delayed drug delivery to colon: A comparison of two dissolution models to assess colonic targeting performance in-vitro","volume":"5","author":"Prabakaran","year":"2012","journal-title":"Int. J. Appl. Res. Nat. Prod."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.progpolymsci.2018.07.005","article-title":"Pharmapolymers in the 21st century: Synthetic polymers in drug delivery applications","volume":"87","author":"Englert","year":"2018","journal-title":"Prog. Polym. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s40005-017-0355-3","article-title":"Development of vildagliptin loaded Eudragit\u00ae microspheres by screening design: In vitro evaluation","volume":"48","author":"Naik","year":"2018","journal-title":"J. Pharm. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/pc.23169","article-title":"Preparation of novel pH-sensitive nanocomposites based on ionic-liquid modified montmorillonite for colon specific drug delivery system","volume":"37","author":"Mahkam","year":"2016","journal-title":"Polym. Compos."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ejpb.2004.01.003","article-title":"Design of pH-sensitive microspheres for the colonic delivery of the immunosuppressive drug tacrolimus","volume":"58","author":"Lamprecht","year":"2004","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.addr.2018.06.021","article-title":"Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art and future perspectives","volume":"146","author":"Kotla","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1166\/jbn.2009.1038","article-title":"Curcumin-loaded pH-sensitive nanoparticles for the treatment of colon cancer","volume":"5","author":"Prajakta","year":"2009","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s12272-020-01219-0","article-title":"Advances in colon-targeted nano-drug delivery systems: Challenges and solutions","volume":"43","author":"Naeem","year":"2020","journal-title":"Arch. Pharmacal. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/star.201000120","article-title":"A novel pH-sensitive hydrogels for potential colon-specific drug delivery: Characterization and in vitro release studies","volume":"63","author":"Liu","year":"2011","journal-title":"Starch-St\u00e4rke"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Mamidi, N., Velasco Delgadillo, R., Gonz\u00e1les Ortiz, A., and Barrera, E.V. (2020). Carbon. nano-onions reinforced multilayered thin film system for stimuli-responsive drug release. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12121208"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Mamidi, N., Velasco Delgadillo, R.M., and Barrera, E.V. (2021). Covalently Functionalized Carbon Nano-Onions Integrated Gelatin Methacryloyl Nanocomposite Hydrogel Containing \u03b3-Cyclodextrin as Drug Carrier for High-Performance PH-Triggered Drug Release. Pharmaceutics, 14, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8064464\/.","DOI":"10.3390\/ph14040291"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.colsurfb.2021.111819","article-title":"Design, fabrication and drug release potential of dual stimuli-responsive composite hydrogel nanoparticle interfaces","volume":"204","author":"Mamidi","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1126\/science.aaw2367","article-title":"The gut microbiota and colon cancer","volume":"364","author":"Garrett","year":"2019","journal-title":"Science"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.carbpol.2011.12.021","article-title":"Carbohydrate polymers: Applications and recent advances in delivering drugs to the colon","volume":"88","author":"Shukla","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_128","first-page":"418","article-title":"Mucoadhesive polymers: Means of improving the mucoadhesive properties of drug delivery system","volume":"2","author":"Yadav","year":"2010","journal-title":"J. Chem. Pharm. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.foodhyd.2018.04.042","article-title":"Preparation and characterization of pectin\/chitosan beads containing porous starch embedded with doxorubicin hydrochloride: A novel and simple colon targeted drug delivery system","volume":"95","author":"Zhu","year":"2019","journal-title":"Food Hydrocoll."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.carbpol.2019.05.067","article-title":"Review of polysaccharide particle-based functional drug delivery","volume":"221","author":"Barclay","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"119013","DOI":"10.1016\/j.carbpol.2021.119013","article-title":"Review on design strategies and considerations of polysaccharide-based smart drug delivery systems for cancer therapy","volume":"279","author":"Meng","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_132","first-page":"3","article-title":"Polysaccharides in colon specific drug delivery","volume":"1","author":"Jain","year":"2015","journal-title":"J. Transl. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/marc.201400406","article-title":"Recent strategies to develop polysaccharide-based nanomaterials for biomedical applications","volume":"35","author":"Wen","year":"2014","journal-title":"Macromol. Rapid Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ejpb.2015.09.012","article-title":"Effect of co-administration of probiotics with polysaccharide-based colon targeted delivery systems to optimize site specific drug release","volume":"97","author":"Prudhviraj","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"7718","DOI":"10.3748\/wjg.v22.i34.7718","article-title":"Recent advances in orally administered cell-specific nanotherapeutics for inflammatory bowel disease","volume":"22","author":"Si","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1021\/acs.jmedchem.0c01530","article-title":"Peptide\u2013drug conjugates with different linkers for cancer therapy","volume":"64","author":"Alas","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"607692","DOI":"10.3389\/fimmu.2021.607692","article-title":"Antibodies targeting the transferrin receptor 1 (tfr1) as direct anti-cancer agents","volume":"12","author":"Candelaria","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Tesauro, D., Accardo, A., Diaferia, C., Milano, V., Guillon, J., Ronga, L., and Rossi, F. (2019). Peptide-based drug-delivery systems in biotechnological applications: Recent advances and perspectives. Molecules, 24.","DOI":"10.3390\/molecules24020351"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s40005-017-0374-0","article-title":"Peptides as drug delivery vehicles across biological barriers","volume":"48","author":"Ghosh","year":"2018","journal-title":"J. Pharm. Investig."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1039\/C8BM01340C","article-title":"Peptide ligand-mediated targeted drug delivery of nanomedicines","volume":"7","author":"Jiang","year":"2019","journal-title":"Biomater. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s40005-018-00424-w","article-title":"Designing a drug delivery system for improved tumor treatment and targeting by functionalization of a cell-penetrating peptide","volume":"49","author":"Masheta","year":"2019","journal-title":"J. Pharm. Investig."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.3109\/10717544.2015.1077293","article-title":"A new peptide ligand for colon cancer targeted delivery of micelles","volume":"23","author":"Ren","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1039\/C8BM01485J","article-title":"Enhanced oral absorption of insulin using colon-specific nanoparticles co-modified with amphiphilic chitosan derivatives and cell-penetrating peptides","volume":"7","author":"Guo","year":"2019","journal-title":"Biomater. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Langel, \u00dc. (2019). Methods for CPP functionalization. CPP Cell-Penetrating Pept., 83\u2013156.","DOI":"10.1007\/978-981-13-8747-0_3"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/bjc.2012.605","article-title":"Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting","volume":"108","author":"Tiernan","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_146","first-page":"100917","article-title":"Folate Receptor as a Biomarker and Therapeutic Target in Solid Tumors","volume":"47","author":"Noe","year":"2022","journal-title":"Curr. Probl. Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"102363","DOI":"10.1016\/j.ctrv.2022.102363","article-title":"HER2 targeted therapy in colorectal cancer: New horizons","volume":"105","author":"Suwaidan","year":"2022","journal-title":"Cancer Treat. Rev."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"6817","DOI":"10.1002\/jcp.29576","article-title":"Hyaluronic acid-decorated liposomal nanoparticles for targeted delivery of 5-fluorouracil into HT-29 colorectal cancer cells","volume":"235","author":"Mansoori","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"108430","DOI":"10.1016\/j.inoche.2020.108430","article-title":"pH-responsive and CD44-targeting by Fe3O4\/MSNs-NH2 nanocarriers for oxaliplatin loading and colon cancer treatment","volume":"125","author":"Tabasi","year":"2021","journal-title":"Inorg. Chem. Commun."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1124\/dmd.112.044925","article-title":"Nano-advantage in enhanced drug delivery with biodegradable nanoparticles: Contribution of reduced clearance","volume":"40","author":"Kadam","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"110975","DOI":"10.1016\/j.msec.2020.110975","article-title":"A new formulation of hydrophobin-coated niosome as a drug carrier to cancer cells","volume":"113","author":"Barani","year":"2020","journal-title":"Mater. Sci. Eng."},{"key":"ref_152","first-page":"1671","article-title":"Niosomal drug delivery systems: Formulation, preparation and applications","volume":"32","author":"Bagheri","year":"2014","journal-title":"World Appl. Sci. J."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fbio.2016.04.005","article-title":"Effect of composition, hydrogenation of phospholipids and lyophilization on the characteristics of eugenol-loaded liposomes prepared by ethanol injection method","volume":"15","author":"Sebaaly","year":"2016","journal-title":"Food Biosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1166\/jcsb.2012.1020","article-title":"Preparation, characterization and applications of liposomes: State of the art","volume":"1","author":"Laouini","year":"2012","journal-title":"J. Colloid. Sci. Biotechnol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Liu, P., Chen, G., and Zhang, J. (2022). A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules, 27.","DOI":"10.3390\/molecules27041372"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.ejpb.2012.02.009","article-title":"Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: The effect of cholate type, particle size and administered dose","volume":"81","author":"Niu","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.colsurfb.2008.11.033","article-title":"Modulation of the physicochemical state of interior agents to prepare controlled release liposomes","volume":"69","author":"Wang","year":"2009","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_158","first-page":"20180032","article-title":"Passive and active targeting in cancer therapy by liposomes and lipid nanoparticles","volume":"34","author":"Alavi","year":"2019","journal-title":"Drug Metab. Pers. Ther."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"8475","DOI":"10.1039\/D1RA00038A","article-title":"In silico and in vitro design of cordycepin encapsulation in liposomes for colon cancer treatment","volume":"11","author":"Khuntawee","year":"2021","journal-title":"RSC Adv."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1080\/02652048.2017.1339739","article-title":"Mannosylated liposomes improve therapeutic effects of paclitaxel in colon cancer models","volume":"34","author":"Xiong","year":"2017","journal-title":"J. Microencapsul."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"121878","DOI":"10.1016\/j.ijpharm.2022.121878","article-title":"A state-of-the-art review on the recent advances of niosomes as a targeted drug delivery system","volume":"624","author":"Yasamineh","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cis.2013.11.018","article-title":"Niosomes from 80s to present: The state of the art","volume":"205","author":"Marianecci","year":"2014","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jconrel.2014.04.015","article-title":"Nano-niosomes as nanoscale drug delivery systems: An illustrated review","volume":"185","author":"Moghassemi","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Varshosaz, J., Taymouri, S., Pardakhty, A., Asadi-Shekaari, M., and Babaee, A. (2014). Niosomes of ascorbic acid and \u03b1-tocopherol in the cerebral ischemia-reperfusion model in male rats. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/816103"},{"key":"ref_165","first-page":"249","article-title":"Preparation and evaluation of niosomes containing aceclofenac","volume":"5","author":"Srinivas","year":"2010","journal-title":"Dig. J. Nanomater. Bios"},{"key":"ref_166","first-page":"1036","article-title":"Niosomes: A novel trend in drug delivery","volume":"3","author":"Shakya","year":"2014","journal-title":"Int. J. Res. Dev. Pharm. Life Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejpb.2019.08.015","article-title":"Recent advances in non-ionic surfactant vesicles (niosomes): Fabrication, characterization, pharmaceutical and cosmetic applications","volume":"144","author":"Chen","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Witika, B.A., Bassey, K.E., Demana, P.H., Siwe-Noundou, X., and Poka, M.S. (2022). Current advances in specialised niosomal drug delivery: Manufacture, characterization and drug delivery applications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179668"},{"key":"ref_169","first-page":"549","article-title":"Niosomes as a novel pharmaceutical formulation encapsulating the hepatoprotective drug silymarin","volume":"4","author":"Badawi","year":"2012","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"s11","DOI":"10.5530\/ijper.55.1s.34","article-title":"Niosome as a novel pharmaceutical drug delivery: A brief review highlighting formulation, types, composition and application","volume":"55","author":"Umbarkar","year":"2021","journal-title":"Indian. J. Pharm. Educ. Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"e12369","DOI":"10.1016\/j.heliyon.2022.e12369","article-title":"The effect of noisome preparation methods in encapsulating 5-fluorouracil and real time cell assay against HCT-116 colon cancer cell line","volume":"8","author":"Ugorji","year":"2022","journal-title":"Heliyon"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"El-Far, S.W., Abo El-Enin, H.A., Abdou, E.M., Nafea, O.E., and Abdelmonem, R. (2022). Targeting colorectal cancer cells with niosomes systems loaded with two anticancer drugs models; comparative in vitro and anticancer studies. Pharmaceuticals, 15.","DOI":"10.3390\/ph15070816"},{"key":"ref_173","first-page":"1001","article-title":"Polymeric nanoparticles for targeted treatment in oncology: Current insights","volume":"10","author":"Prabhu","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrgastro.2015.37","article-title":"Nanomedicines in gastroenterology and hepatology","volume":"12","author":"Lamprecht","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-1-60761-609-2_3","article-title":"Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting","volume":"624","author":"Greish","year":"2010","journal-title":"Cancer Nanotechnol. Methods Protoc."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Ejigah, V., Owoseni, O., Bataille-Backer, P., Ogundipe, O.D., Fisusi, F.A., and Adesina, S.K. (2022). Approaches to improve macromolecule and nanoparticle accumulation in the tumor microenvironment by the enhanced permeability and retention effect. Polymers, 14.","DOI":"10.3390\/polym14132601"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.2217\/fon-2020-1238","article-title":"Trifluridine\/tipiracil plus bevacizumab for third-line management of metastatic colorectal cancer: SUNLIGHT study design","volume":"17","author":"Tabernero","year":"2021","journal-title":"Future Oncol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1056\/NEJMoa2214963","article-title":"Trifluridine\u2013tipiracil and bevacizumab in refractory metastatic colorectal cancer","volume":"388","author":"Prager","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1038\/s41416-023-02212-2","article-title":"Trifluridine\/tipiracil+ bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+ BEV as second-line therapy for metastatic colorectal cancer: A randomised noninferiority trial","volume":"128","author":"Kuboki","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0140-6736(23)00772-9","article-title":"Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (fresco-2): An International, multicentre, randomised, double-blind, phase 3 study","volume":"402","author":"Dasari","year":"2023","journal-title":"Lancet"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.1158\/0008-5472.CAN-19-0566","article-title":"Cancer and the circadian clock","volume":"79","author":"Shafi","year":"2019","journal-title":"Cancer Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41568-020-0291-9","article-title":"Metabolic rivalry: Circadian homeostasis and tumorigenesis","volume":"20","author":"Kinouchi","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"741295","DOI":"10.3389\/fphar.2021.741295","article-title":"New insights into cancer chronotherapies","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_184","first-page":"e171","article-title":"Efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer: A systematic review and meta-analysis","volume":"13","author":"Huang","year":"2016","journal-title":"Asia-Pac. J. Clin. Oncol."},{"key":"ref_185","first-page":"e36522","article-title":"Chronomodulated Administration of Chemotherapy in Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis","volume":"15","author":"Nassar","year":"2023","journal-title":"Cureus"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/11\/2620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:21:55Z","timestamp":1760131315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/11\/2620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,12]]},"references-count":185,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["pharmaceutics15112620"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15112620","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,12]]}}}