Insights into the role of the intestinal microbiota in colon cancer

The intestinal microbiota consists of a dynamic organization of bacteria, viruses, archaea, and fungal species essential for maintaining gut homeostasis and protecting the host against pathogenic invasion. When dysregulated, the intestinal microbiota can contribute to colorectal cancer development. Though the microbiota is multifaceted in its ability to induce colorectal cancer, this review will focus on the capability of the microbiota to induce colorectal cancer through the modulation of immune function and the production of microbial-derived metabolites. We will also explore an experimental technique that is revolutionizing intestinal research. By elucidating the interactions of microbial species with epithelial tissue, and allowing for drug screening of patients with colorectal cancers, organoid development is a novel culturing technique that is innovating intestinal research. As a cancer that remains one of the leading causes of cancer-related deaths worldwide, it is imperative that scientific findings are translated into the creation of effective therapeutics to treat colorectal cancer.

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PI3K/ Akt/ mTOR Pathway as a Therapeutic Target for Colorectal Cancer: A Review of Preclinical and Clinical Evidence

Current Drug Targets ◽

10.2174/1389450120666190618123846 ◽

2019 ◽

Vol 20 (12) ◽

pp. 1217-1226 ◽

Cited By ~ 14

Author(s):

Arunaksharan Narayanankutty

Keyword(s):

Colorectal Cancer ◽

Drug Resistance ◽

Therapeutic Target ◽

Clinical Evidence ◽

Mtor Pathway ◽

Colorectal Cancers ◽

Patent Literature ◽

Mtor Signalling ◽

Natural And Synthetic

Background: Phosphoinositide 3-kinase (PI3Ks) is a member of intracellular lipid kinases and involved in the regulation of cellular proliferation, differentiation and survival. Overexpression of the PI3K/Akt/mTOR signalling has been reported in various forms of cancers, especially in colorectal cancers (CRC). Due to their significant roles in the initiation and progression events of colorectal cancer, they are recognized as a striking therapeutic target. Objective: The present review is aimed to provide a detailed outline on the role of PI3K/Akt/mTOR pathway in the initiation and progression events of colorectal cancers as well as its function in drug resistance. Further, the role of PI3K/Akt/mTOR inhibitors alone and in combination with other chemotherapeutic drugs, in alleviating colorectal cancer is also discussed. The review contains preclinical and clinical evidence as well as patent literature of the pathway inhibitors which are natural and synthetic in origin. Methods: The data were obtained from PubMed/Medline databases, Scopus and Google patent literature. Results: PI3K/Akt/mTOR signalling is an important event in colorectal carcinogenesis. In addition, it plays significant roles in acquiring drug resistance as well as metastatic initiation events of CRCs. Several small molecules of natural and synthetic origin have been found to be potent inhibitors of CRCs by effectively downregulating the pathway. Data from various clinical studies also support these pathway inhibitors and several among them are patented. Conclusion: Inhibitors of the PI3K/mTOR pathway have been successful for the treatment of primary and metastatic colorectal cancers, rendering the pathway as a promising clinical cancer therapeutic target.

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Serrated polyposis syndrome and the role of serrated polyps in colorectal cancer development

Colorectal Cancer ◽

10.2217/crc.11.8 ◽

2012 ◽

Vol 1 (1) ◽

pp. 37-47

Author(s):

Karam Singh Boparai ◽

Yark Hazewinkel ◽

Evelien Dekker

Keyword(s):

Colorectal Cancer ◽

Cancer Development ◽

Polyposis Syndrome ◽

Serrated Polyps

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Synchronous NET and colorectal cancer development: a case report

Surgical Case Reports ◽

10.1186/s40792-020-0777-4 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Shinsei Yumoto ◽

Yuji Miyamoto ◽

Takahiko Akiyama ◽

Yuki Kiyozumi ◽

Kojiro Eto ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Systemic Therapy ◽

Multiple Organ ◽

Cancer Development ◽

Sigmoid Colon Cancer ◽

Synchronous Tumors ◽

Case Presentation ◽

The Difference ◽

Rectal Neuroendocrine Tumor

Abstract Background The incidence of synchronous gastrointestinal neuroendocrine tumors (GI-NETs) and colorectal cancer is very low. Case presentation We present a 72-year-old man diagnosed with a rectal neuroendocrine tumor (NET) with multiple organ metastases and simultaneous sigmoid colon cancer. Although the NET was his prognostic factor, he underwent a laparoscopic sigmoidectomy at first because it was expected that the colon cancer would cause obstruction or bleeding during NET treatment. Subsequently, he started taking everolimus. Conclusions We should consider surgical resection of the synchronous cancer before systemic therapy for a GI-NET regardless of the difference in prognosis between synchronous tumors, if the cancer may impair the continuation of systemic therapy.

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Adenosquamous Carcinoma of the Colon

Case Reports in Gastroenterology ◽

10.1159/000485558 ◽

2018 ◽

Vol 11 (3) ◽

pp. 791-796 ◽

Cited By ~ 4

Author(s):

Tagore Sunkara ◽

Megan E Caughey ◽

Priyanka Makkar ◽

Febin John ◽

Vinaya Gaduputi

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Adenosquamous Carcinoma ◽

Colorectal Cancers ◽

Men And Women ◽

Carcinoma Of The Colon ◽

The Third

Overall, colorectal cancer is the third most commonly diagnosed cancer in both men and women, meaning that it is one of the more widely recognized preventable cancers. Instances of colorectal malignancies though are overwhelmingly attributable to adenocarcinoma. Colorectal cancers with components of squamous cell carcinoma represent a statistical anomaly. Here, we present the case of a 50-year-old male, who complained of abdominal pain and weight loss over a 3-month period of time. Biopsies from a colonoscopy ultimately revealed that this patient’s colon cancer consisted of both adenocarcinoma and squamous cell carcinoma, representing a truly exceptional pathology finding in a patient diagnosed with a colorectal cancer.

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Study protocol on the role of intestinal microbiota in colorectal cancer treatment: a pathway to personalized medicine 2.0

International Journal of Colorectal Disease ◽

10.1007/s00384-017-2819-3 ◽

2017 ◽

Vol 32 (7) ◽

pp. 1077-1084 ◽

Cited By ~ 8

Author(s):

R. Aarnoutse ◽

J. M. P. G. M. de Vos-Geelen ◽

J. Penders ◽

E. G. Boerma ◽

F. A. R. M. Warmerdam ◽

...

Keyword(s):

Colorectal Cancer ◽

Personalized Medicine ◽

Cancer Treatment ◽

Intestinal Microbiota ◽

Study Protocol ◽

Medicine 2.0 ◽

Colorectal Cancer Treatment

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The Role of the Gut Microbiome in Colorectal Cancer

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0037-1602239 ◽

2018 ◽

Vol 31 (03) ◽

pp. 192-198 ◽

Cited By ~ 14

Author(s):

Grace Chen

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Microbial Community ◽

Gut Microbiota ◽

Gut Microbiome ◽

Intestinal Health ◽

Genotoxic Effects ◽

Bacterial Populations ◽

Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

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Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽

10.1038/onc.2015.365 ◽

2015 ◽

Vol 35 (24) ◽

pp. 3151-3162 ◽

Cited By ~ 16

Author(s):

Q Zhang ◽

T Wei ◽

K Shim ◽

K Wright ◽

K Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Colon Cancer Cells ◽

Mesenchymal Transition ◽

E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

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The correlation between intestinal microbiota and colorectal cancer

Clinical Medicine (Russian Journal) ◽

10.30629/0023-2149-2021-99-5-6-339-341 ◽

2021 ◽

Vol 99 (5-6) ◽

pp. 339-341

Author(s):

E. M. Lipnitsky ◽

Yu. S. Medkova ◽

E. A. Akhmetgalieva ◽

D. N. Borisova

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Early Diagnosis ◽

Intestinal Microbiota ◽

Intestinal Microflora ◽

Tumor Formation ◽

Oral Microbiota ◽

Qualitative Composition ◽

Oral Microflora ◽

Identification Of Species

The study of intestinal and oral microflora and their metabolites playing an important role in intestinal homeostasis, has led to the identification of species closely related to the development of colorectal cancer, intracellular correlations of fungi and bacteria compared to control. The correlation between oral microbiota and intestinal microflora, as well as associated with the mucous membrane of the large intestine, was revealed. It was noted that the use of eu- and probiotics improved the immunological indices and the structure of the intestinal microbiota. Thus, studying the oral and intestinal microbiota and its metabolites may prove to be a simple, accessible and informative method for the early diagnosis of colon cancer. However, most studies indicate only changes in the quantitative and qualitative composition of the microbiota, hardly revealing its cause-effect relations with the processes of tumor formation in the colon. Therefore, it is necessary to continue studies of this problem.

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