Promising Targets and Drugs in Development for Colorectal Cancer

Thompson, Chris; Leong, Stephen; Messersmith, Wells A.

doi:10.1053/j.seminoncol.2011.05.013

Cited by 3 publications

(3 citation statements)

References 79 publications

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“…Among the eleven MSI patients, we found that two patients with advanced cancer stage III would not respond to the sirolimus treatment, while the remaining nine MSI patients would. In general, the predictions are in agreement with the results from the aforementioned studies [47, 48]. Further, our results support the finding that the prognosis for MSI tumors in stage III CRC is poor [49].…”

Section: Resultssupporting

confidence: 92%

“…At the moment, data on clinical response for these patients is still not available. But our result is in accordance with clinical knowledge that MSI status is related to the response of the treatment under study [47,48]. Based on our results, we strongly hypothesize that one molecular reason for better therapeutic outcomes of MSI patients could be the upregulation of tumor-suppressor miRs and downregulation of oncogenic miRs, which drives the cellular system of patients with MSI status away from the full-fledged malignant cellular state with strong drug resistance and uncontrolled proliferation.…”

Section: Conclusion and Discussionsupporting

confidence: 90%

“…From the Cancer Genome Atlas [46], we obtained genetic data, including miRNA/gene-expression data and patient information (age, sex, race, cancer stage and other) of 22 colon cancer patients (Additional file 3), of which eleven have MSS status, and eleven MSI; the patients' cancer stages range from I to III. Further, two recent studies demonstrated that both drugs sirolimus and LY294002 (targeting mTor- and PI3K-signaling pathways, respectively) clearly reduced the growth of MSI tumors, but not MSS tumors [47, 48]. In order to investigate this issue with the application of the NSAID-miR model, we initialized the model with the gene-expression and miRNA-expression data of these patients individually (Methods).…”

Section: Resultsmentioning

confidence: 99%

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A microRNA molecular modeling extension for prediction of colorectal cancer treatment

Mansmann

2015

BMC Cancer

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BackgroundSeveral studies show that the regulatory impact of microRNAs (miRNAs) is an essential contribution to the pathogenesis of colorectal cancer (CRC). The expression levels of diverse miRNAs are associated with specific clinical diagnoses and prognoses of CRC. However, this association reveals very little actionable information with regard to how or whether to treat a CRC patient. To address this problem, we use miRNA expression data along with other molecular information to predict individual response of CRC cell lines and CRC patients.MethodsA strategy has been developed to join four types of information: molecular, kinetic, genetic and treatment data for prediction of individual treatment response of CRC.ResultsInformation on miRNA regulation, including miRNA target regulation and transcriptional regulation of miRNA, in integrated into an in silico molecular model for colon cancer. This molecular model is applied to study responses of seven CRC cell lines from NCI-60 to ten agents targeting signaling pathways. Predictive results of models without and with implemented miRNA information are compared and advantages are shown for the extended model. Finally, the extended model was applied to the data of 22 CRC patients to predict response to treatments of sirolimus and LY294002. The in silico results can also replicate the oncogenic and tumor suppression roles of miRNA on the therapeutic response as reported in the literature.ConclusionsIn summary, the results reveal that detailed molecular events can be combined with individual genetic data, including gene/miRNA expression data, to enhance in silico prediction of therapeutic response of individual CRC tumors. The study demonstrates that miRNA information can be applied as actionable information regarding individual therapeutic response.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1437-0) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 92%

Section: Conclusion and Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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A microRNA molecular modeling extension for prediction of colorectal cancer treatment

Mansmann

2015

BMC Cancer

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Involvement of Autophagy and Apoptosis in Studies of Anticancer Drugs

Liu¹,

Ouyang²

2014

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

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Novel drug discovery opportunities for colorectal cancer

Curtin

2013

Expert Opinion on Drug Discovery

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Despite recent advances including the introduction of targeted therapeutics, prognosis for advanced CRC patients remains bleak, reinforcing the need for novel therapeutic intervention. Developmental pathways such as Notch and Wnt provide opportunities to address this urgent need, and preclinical evidence supports targeting these pathways in CRC. Progress has been made toward this end, and while challenges persist, an increasing number of preclinical findings show promise.

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Promising Targets and Drugs in Development for Colorectal Cancer

Cited by 3 publications

References 79 publications

A microRNA molecular modeling extension for prediction of colorectal cancer treatment

A microRNA molecular modeling extension for prediction of colorectal cancer treatment

Involvement of Autophagy and Apoptosis in Studies of Anticancer Drugs

Novel drug discovery opportunities for colorectal cancer

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