Role of Genomic Markers in Colorectal Cancer Treatment

For the last four decades, fluorouracil (FU) has been the main treatment of choice in colorectal cancer (CRC) in both the advanced and adjuvant settings. In the advanced setting, FU monotherapy produces response rates of only 10% to 20%. Furthermore, in resected stage III CRC, FU monotherapy has increased overall survival by only 20%. The combination of FU with newer therapies such as oxaliplatin and irinotecan has significantly improved response rates to 40% to 50%. Despite these improvements, more than half of advanced CRC patients derive no benefit from treatment; this is due to either acquired or inherent drug resistance. This review aims to highlight the current prognostic and predictive markers that have been identified for CRC to date. The limited use of these predictive markers underscores the importance of and need for multiple marker testing in order to improve response rates and decrease toxicity. This review will also focus on high throughput methods to identify panels of predictive markers for CRC, which ultimately aim to tailor treatment according to an individual patient and tumor profile.

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Exosomal microRNAs and other non-coding RNAs as colorectal cancer biomarkers: a review

Mutagenesis ◽

10.1093/mutage/gez038 ◽

2019 ◽

Vol 35 (3) ◽

pp. 243-260 ◽

Cited By ~ 6

Author(s):

Antonio Francavilla ◽

Szimonetta Turoczi ◽

Sonia Tarallo ◽

Pavel Vodicka ◽

Barbara Pardini ◽

...

Keyword(s):

Colorectal Cancer ◽

Expression Profiles ◽

Predictive Markers ◽

Circular Rnas ◽

Rna Molecules ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Prognostic And Predictive Markers

Abstract The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.

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Prognostic and Predictive Markers in Colorectal Cancer – The Role of New Genomic Technologies

Current Pharmacogenomics ◽

10.2174/157016007782793728 ◽

2007 ◽

Vol 5 (4) ◽

pp. 255-261

Author(s):

Vicky Coyle ◽

Wendy Allen ◽

Daniel Longley ◽

Patrick Johnston

Keyword(s):

Colorectal Cancer ◽

Predictive Markers ◽

Genomic Technologies ◽

Prognostic And Predictive Markers

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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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Role ofNRASmutations as prognostic and predictive markers in metastatic colorectal cancer

International Journal of Cancer ◽

10.1002/ijc.28955 ◽

2014 ◽

Vol 136 (1) ◽

pp. 83-90 ◽

Cited By ~ 64

Author(s):

Marta Schirripa ◽

Chiara Cremolini ◽

Fotios Loupakis ◽

Manfredi Morvillo ◽

Francesca Bergamo ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Predictive Markers ◽

Prognostic And Predictive Markers

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The Regulatory Role of Both MBNL1 and MBNL1-AS1 in Several Common Cancers

Current Pharmaceutical Design ◽

10.2174/1381612827666210830110732 ◽

2021 ◽

Vol 27 ◽

Author(s):

Qi Zhang ◽

Yinxin Wu ◽

Jinlan Chen ◽

Yuxuan Cai ◽

Bei Wang ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Gastric Cancer ◽

Lung Cancer ◽

Overall Survival ◽

Survival Rate ◽

Rna Splicing ◽

Metabolic Regulation ◽

Overall Survival Rate

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer. Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers. Methods: It was searched by the PUMUB system and summarized its expression in various cancers. Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased. Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.

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