scholarly journals Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine

2020 ◽  
Vol 9 (9) ◽  
pp. 2852
Author(s):  
Giuseppe Sammarco ◽  
Gaetano Gallo ◽  
Giuseppina Vescio ◽  
Arcangelo Picciariello ◽  
Gilda De Paola ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mast Cells ◽  
Precision Medicine ◽  
Cost Effective ◽  
Normal Mucosa ◽  
Improve Patient Survival ◽  
Non Invasive ◽  
Therapy Targets ◽  
Oncogene Homologue

Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called “ideal biomarkers”, for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine.

Use of Circulating Cell-Free DNA to Guide Precision Medicine in Patients with Colorectal Cancer

2021 ◽  
Vol 72 (1) ◽  
pp. 399-413
Author(s):  
Van K. Morris ◽  
John H. Strickler
Keyword(s):  
Colorectal Cancer ◽  
Precision Medicine ◽  
Residual Disease ◽  
Cost Effective ◽  
Patient Specific ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Metastatic Setting ◽  
Diagnostic Technology

Patient-specific biomarkers form the foundation of precision medicine strategies. To realize the promise of precision medicine in patients with colorectal cancer (CRC), access to cost-effective, convenient, and safe assays is critical. Improvements in diagnostic technology have enabled ultrasensitive and specific assays to identify cell-free DNA (cfDNA) from a routine blood draw. Clinicians are already employing these minimally invasive assays to identify drivers of therapeutic resistance and measure genomic heterogeneity, particularly when tumor tissue is difficult to access or serial sampling is necessary. As cfDNA diagnostic technology continues to improve, more innovative applications are anticipated. In this review, we focus on four clinical applications for cfDNA analysis in the management of CRC: detecting minimal residual disease, monitoring treatment response in the metastatic setting, identifying drivers of treatment sensitivity and resistance, and guiding therapeutic strategies to overcome resistance.

scholarly journals Role of colonoscopy in colorectal cancer

2001 ◽  
Vol 56 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Sergio Eduardo Alonso Araujo ◽  
Paulo Roberto Arruda Alves ◽  
Angelita Habr-Gama
Keyword(s):  
Colorectal Cancer ◽  
Cost Effective ◽  
Risk Groups ◽  
Premalignant Lesions ◽  
Average Risk ◽  
Colonoscopic Polypectomy ◽  
Histologic Diagnosis ◽  
Improvement In Survival ◽  
Common Malignancy

Colorectal cancer (CRC) represents the third most common malignancy throughout the world. Little or no improvement in survival has been effectively achieved in the last 50 years. Extensive epidemiological and genetic data are able to identify more precisely definite risk-groups so screening and early diagnosis can be more frequently accomplished. CRC is best detected by colonoscopy, which allows sampling for histologic diagnosis. Colonoscopy is the gold standard for detection of small and premalignant lesions, although it is not cost-effective for screening average-risk population. Colonoscopic polypectomy and mucosal resection constitute curative treatment for selective cases of invasive CRC. Similarly, alternative trans-colonoscopic treatment can be offered for adequate palliation, thus avoiding surgery.

High Expression of sLex Associated with Poor Survival in Argentinian Colorectal Cancer Patients

2014 ◽  
Vol 29 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Ariel Zwenger ◽  
Martin Rabassa ◽  
Sandra Demichelis ◽  
Gabriel Grossman ◽  
Amada Segal-Eiras ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Normal Mucosa ◽  
Poor Survival ◽  
Primary Tumors ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Colorectal Cancer Patients

Aim Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. Methods Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. Results In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (p<0.05). A multiple comparison analysis showed that MUC1 and sLex discriminated among 3 groups: normal, adenoma, and CRC tissues. The increase of sLex expression showed an association with recurrence, and survival analysis showed that a high sLex staining was significantly associated with a poor survival. By multivariate analysis MUC1 inmunoreactivity correlated positively and significantly with tumor size, while MUC2 expression showed the opposite correlation. Conclusions The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.

scholarly journals Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Luciana Petti ◽  
Giulia Rizzo ◽  
Federica Rubbino ◽  
Sudharshan Elangovan ◽  
Piergiuseppe Colombo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Tumor Suppressor ◽  
Normal Mucosa ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Sphingosine 1 Phosphate

Abstract Background Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap. Methods We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice. Results S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/− mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN. Conclusions In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5. Graphical Abstract. Schematic drawing of the role of S1PR2 in normal mucosa and colorectal cancer. In the normal mucosa, S1PR2 is highly expressed by differentiated cells at the upper region of both colon and intestinal crypts (S1PR2 ON), but not by the undifferentiated stem cell at the base of the crypts (S1PR2 OFF), in which acts as a negative proliferative regulator promoting epithelial differentiation. Its loss leads to the expansion of stem cells and reduced levels of PTEN and Axin-2, two negative regulators respectively of PI3K/AKT and Wnt signaling that control β-catenin signaling. The translocation of β-catenin into the nucleus promotes the transcription of target genes involved in the proliferation and malignant transformation. Thereby, S1PR2 works in the intestine as a tumor suppressor

Tu1913 Towards the Non-Invasive Detection of Colorectal Cancer: The Role of Electronic Noses (E-Nose) and Faims

2013 ◽  
Vol 144 (5) ◽  
pp. S-879
Author(s):  
James Covington ◽  
Eric W Westenbrink ◽  
Nicola C. O'Connell ◽  
Catherine Bailey ◽  
Mathew Thomas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Electronic Noses ◽  
Non Invasive

scholarly journals Role of mast cells in colorectal cancer development, the jury is still out

2012 ◽  
Vol 1822 (1) ◽  
pp. 9-13 ◽  
Author(s):  
J. Heijmans ◽  
N.V. Büller ◽  
V. Muncan ◽  
G.R. van den Brink
Keyword(s):  
Colorectal Cancer ◽  
Mast Cells ◽  
Cancer Development

scholarly journals Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors

2004 ◽  
Vol 20 (4-5) ◽  
pp. 207-213 ◽  
Author(s):  
H. F. A. Vasen ◽  
Y. Hendriks ◽  
A. E. de Jong ◽  
M. van Puijenbroek ◽  
C. Tops ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endometrial Cancer ◽  
Gene Mutation ◽  
Molecular Analysis ◽  
Cost Effective ◽  
Preventative Measures ◽  
Amsterdam Criteria ◽  
Revised Amsterdam Criteria ◽  
Msi Analysis

Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI) in tumors. The Bethesda guidelines have been proposed for the identification of families suspected of HNPCC that require further molecular analysis. We have evaluated the yield of MSI-analysis in a large series of Dutch families suspected of HNPCC. We also analysed whether the loss of mismatch repair (MMR) protein detected by immunohistochemistry (IHC) of colorectal cancer (CRC) and endometrial cancer correlated with the presence of MSI and/or a MMR gene mutation. The results showed that the Bethesda criteria with a few modifications are appropriate to identify families eligible for genetic testing. In addition, we found that MSI and IHC-analysis of CRC using antibodies against MLH1, MSH2, MSH6 and PMS2 proteins are equally effective for identifying carriers of the known MMR gene defects. However, as long as the role of other putative MMR genes in hereditary CRC has not been elucidated, IHC-analysis cannot completely replace MSI. For this reason, we prefer MSI-analysis as first step in families suspected of HNPCC. On the other hand, in families fulfilling the revised Amsterdam criteria in which the probability of detecting a mutation is relatively high, we would recommend IHC as first diagnostic step because the result might predict the specific underlying MMR gene mutation. MSI or IHC-analysis of endometrial cancer alone was found to be less sensitive compared with these tests performed in colorectal cancer. Therefore, probably the best approach in the analysis of this cancer is to perform both techniques. The identification of HNPCC is important as it makes it possible to target effective preventative measures. Our studies showed that MSI and IHC analysis of colorectal and endometrial cancer, are reliable cost-effective tools that can be used to identify patients with HNPCC.

scholarly journals S263 Role of Demographics in Non-Invasive Testing for Colorectal Cancer Screening: Do Targeted Cut-Off Values Improve Detection?

2021 ◽  
Vol 116 (1) ◽  
pp. S117-S117
Author(s):  
Inayat Gill ◽  
Christienne Shams ◽  
Angy Hanna ◽  
Julie George ◽  
Laith H. Jamil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Non Invasive

scholarly journals Screening and prevention of colorectal cancer

BMJ ◽  
2021 ◽  
pp. n1855
Author(s):  
Priyanka Kanth ◽  
John M Inadomi
Keyword(s):  
Colorectal Cancer ◽  
New Technologies ◽  
Current Status ◽  
Non Invasive ◽  
The Past ◽  
The Us ◽  
Screening And Prevention ◽  
Current Emphasis

Abstract Mortality from colorectal cancer is reduced through screening and early detection; moreover, removal of neoplastic lesions can reduce cancer incidence. While understanding of the risk factors, pathogenesis, and precursor lesions of colorectal cancer has advanced, the cause of the recent increase in cancer among young adults is largely unknown. Multiple invasive, semi- and non-invasive screening modalities have emerged over the past decade. The current emphasis on quality of colonoscopy has improved the effectiveness of screening and prevention, and the role of new technologies in detection of neoplasia, such as artificial intelligence, is rapidly emerging. The overall screening rates in the US, however, are suboptimal, and few interventions have been shown to increase screening uptake. This review provides an overview of colorectal cancer, the current status of screening efforts, and the tools available to reduce mortality from colorectal cancer.

Advances in early detection of colorectal cancer: A focus on non-invasive biomarkers

2021 ◽  
Vol 22 ◽  
Author(s):  
Nadia El Kadmiri
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Secondary Outcome ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Biomarker Analysis ◽  
Genomic Markers ◽  
Bibliographic Search ◽  
Noninvasive Tests

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer Worldwide. Currently, colonoscopy remains the gold standard diagnostic test for CRC detection. Nonetheless, this technique is invasive and expensive. Remarkable ongoing strategies are focusing on development affordable methods to diagnosis at earlier stages and surveille CRC. The introduction of suitable noninvasive, sensitive and specified diagnostic tests for early CRC detection by employing biomarker analysis seems to be a fundamental need to reduce the numbers of unnecessary colonoscopies. In this Review, we provide an overview of single- and multi-panel biomarkers (Genomic markers, transcriptome markers, proteomic markers, inflammatory markers and microbiome markers) encompassing noninvasive tests in blood and stool for early CRC detection. Methods: A bibliographic search using PubMed/Medline, Web of Science and EBSCOhost databases was performed to find relevant published studies over the last 6 years. Forty-three pertinent studies were included in this review. Results: The primary outcome highlights the sensitivity and specificity of single diagnostic biomarkers studied in blood or stool. The secondary outcome reveals the sensitivity and specificity of panel -biomarkers (combinations) in blood or stool. While some markers show better performance, other are not suitable for screening purposes. Conclusion: It remains to adjust experimental and analytical tests that can interfere à robust results to replace or supplement those currently markers in use. Even so, robust verification and validation with large clinical cohorts are needed to successful noninvasive tests that can fulfill the role of colonoscopy.

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