Metastatic Colorectal Cancer in the Era of Personalized Medicine: A More Tailored Approach to Systemic Therapy

Yu, Irene S.; Cheung, Winson Y.

doi:10.1155/2018/9450754

Cited by 38 publications

(37 citation statements)

References 105 publications

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“…However, these clinicopathological characteristics do not provide sufficiently accurate information, which may result in incorrect prognosis judgements. Patients at low risk might receive excessive or unnecessary treatment, whereas others may progress to metastasis or relapse because of insufficient treatment [8] . Thus, it is important to find new molecular markers for predicting the prognosis of patients with CRC and determining the appropriate treatment.…”

Section: Ivyspringmentioning

confidence: 99%

Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer

et al. 2021

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Colorectal cancer (CRC) is a commonly occurring tumour with poor prognosis. Autophagy-related long non-coding RNAs (lncRNAs) have received much attention as biomarkers for cancer prognosis and diagnosis. However, few studies have focused on their prognostic predictive value specifically in CRC. This research aimed to construct a robust autophagy-related lncRNA prognostic signature for CRC. Autophagy-related lncRNAs from The Cancer Genome Atlas database were screened using univariate Cox, LASSO, and multivariate Cox regression analyses, and the resulting key lncRNAs were used to establish a prognostic risk score model. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression of several lncRNAs in cancer tissues from CRC patients and in normal tissues adjacent to the cancer tissues. A prognostic signature comprising lncRNAs AC125603.2, LINC00909, AC016876.1, MIR210HG, AC009237.14, and LINC01063 was identified in patients with CRC. A graphical nomogram based on the autophagy-related lncRNA signature was developed to predict CRC patients' 1-, 3-, and 5-year survival. Overall survival in patients with low risk scores was significantly better than in those with high risk scores (P < 0.0001); a similar result was obtained in an internal validation sample. The nomogram was shown to be suitable for clinical use and gave correct predictions. The 1-and 3-year values of the area under the receiver operating characteristic curve were 0.797 and 0.771 in the model sample, and 0.656 and 0.642 in the internal validation sample, respectively. The C-index values for the verification samples and training samples were 0.756 (95% CI = 0.668-0.762) and 0.715 (95% CI = 0.683-0.829), respectively. Gene set enrichment analysis showed that the six autophagy-related lncRNAs were greatly enriched in CRC-related signalling pathways, including p53 and VEGF signalling. The qRT-PCR results showed that the expression of lncRNAs in CRC was higher than that in adjacent tissues, consistent with the expression trends of lncRNAs in the CRC data set. In summary, we established a signature of six autophagy-related lncRNAs that could effectively guide clinical prediction of prognosis in patients with CRC. This lncRNA signature has significant clinical implications for improving the prediction of outcomes and, with further prospective validation, could be used to guide tailored therapy for CRC patients.

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Section: Ivyspringmentioning

confidence: 99%

Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer

et al. 2021

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“…Successful treatment of these malignancies largely depends on effective screening tools, such as diagnostic blood, stool and endoscopic tests [3][4][5]. Therapeutic approaches include surgery, chemo and radiation therapy, hormone therapy; as well as tailored and personalized therapies, which are presently undergoing development [6][7][8][9][10][11][12][13]. To further advance personalized medicine, many research groups have focused their work on the understanding of the molecular nature of cancer hallmark functions, including unlimited proliferation, increased viability, migration and invasion of cancer cells, and decreased ability to induce apoptosis [14].…”

Section: Introductionmentioning

confidence: 99%

TRP Channels in Digestive Tract Cancers

Stokłosa

Borgström

Kappel

et al. 2020

IJMS

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Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets.

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“…In spite of major advances, the 5-year survival rate for patients with metastatic disease remains at 15% [2]. Pharmacotherapy for mCRC has evolved over time, from the initial regimen of 5-FU/Leucovorin to the current standard of care of FOLFOX or FOLFIRI, with anti-VEGF (e.g., bevacizumab), anti-EGFR (e.g., cetuximab) molecules also being integrated into treatment protocols [3]. Additionally, the approvals in 2017 of PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab for patients with a sub-type of CRC (mismatch repair deficient, dMMR) [4] has further expanded the therapeutic armamentarium.…”

Section: Introductionmentioning

confidence: 99%

Immune characterization of metastatic colorectal cancer patients post reovirus administration

et al. 2020

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Background: KRAS mutations are prevalent in 40-45% of patients with colorectal cancer (CRC) and targeting this gene has remained elusive. Viruses are well known immune sensitizing agents. The therapeutic efficacy of oncolytic reovirus in combination with chemotherapy is examined in a phase 1 study of metastatic CRC. This study evaluates the nature of immune response by determining the cytokine expression pattern in peripheral circulation along with the distribution of antigen presenting cells (APCs) and activated T lymphocytes. Further the study evaluates the alterations in exosomal and cellular microRNA levels along with the effect of reovirus on leukocyte transcriptome. Methods: Reovirus was administered as a 60-min intravenous infusion for 5 consecutive days every 28 days, at a tissue culture infective dose (TCID 50) of 3 × 10 10. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood prior to reovirus administration and post-reovirus on days 2, 8, and 15. The expression profile of 25 cytokines in plasma was assessed (post PBMC isolation) on an EMD Millipore multiplex Luminex platform. Exosome and cellular levels of miR-29a-3p was determined in pre and post reovirus treated samples. Peripheral blood mononuclear cells were stained with fluorophore labelled antibodies against CD4, CD8, CD56, CD70, and CD123, fixed and evaluated by flow cytometry. The expression of granzyme B was determined on core biopsy of one patient. Finally, Clariom D Assay was used to determine the expression of 847 immune-related genes when compared to pre reovirus treatment by RNA sequencing analysis. A change was considered if the expression level either doubled or halved and the significance was determined at a p value of 0.001.

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Metastatic Colorectal Cancer in the Era of Personalized Medicine: A More Tailored Approach to Systemic Therapy

Cited by 38 publications

References 105 publications

Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer

Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer

TRP Channels in Digestive Tract Cancers

Immune characterization of metastatic colorectal cancer patients post reovirus administration

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