Role of γ-glutamyl cyclotransferase as a therapeutic target for colorectal cancer based on the lentivirus-mediated system

2016 ◽  
Vol 27 (10) ◽  
pp. 1011-1020 ◽  
Author(s):  
Jian Dong ◽  
Yuanhang Zhou ◽  
Zhiwei Liao ◽  
Qi Huang ◽  
Shidong Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Target

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

2019 ◽  
Vol 20 (12) ◽  
pp. 1217-1226 ◽  
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.

scholarly journals The role of Reg IV in colorectal cancer, as a potential therapeutic target

2015 ◽  
Vol 4 ◽  
pp. 261-264
Author(s):  
Yiwang Hu ◽  
Chi Pan ◽  
Jiyi Hu ◽  
Suzhan Zhang
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals Hsa_circRNA_002144 promotes growth and metastasis of colorectal cancer through regulating miR-615-5p/LARP1/mTOR pathway

2020 ◽  
Author(s):  
Mengqiong Wu ◽  
Cancan Kong ◽  
Manni Cai ◽  
Weiwei Huang ◽  
Yiming Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Target ◽  
Poor Prognosis ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Over Expression ◽  
Functional Assays ◽  
Cancer Intervention

Abstract CircRNAs (circular RNAs), recently identified as a critical regulator in tumorigenesis, participate in colorectal cancer (CRC) growth. However, role of hsa_circRNA_002144 in CRC was poorly understood. Firstly, hsa_circRNA_002144 showed significantly elevation in both of CRC tissues and cell lines, and suggested closely associated with poor prognosis in patients. Secondly, data from functional assays revealed that silence of hsa_circRNA_002144 inhibited CRC progression with reduced cell viability, proliferation, migration and invasion, while enhanced cell apoptosis. In addition, in vivo CRC growth and metastasis were also suppressed by knockdown of hsa_circRNA_002144. However, CRC progression was promoted with over-expression of hsa_circRNA_002144. Thirdly, hsa_circRNA_002144 colocalized with miR-615-5p in the cytoplasm of CRC cells, and decreased miR-615-5p expression. Moreover, miR-615-5p could target LARP1 (La ribonucleoprotein 1, translational regulator). Lastly, the suppressive effects of hsa_circRNA_002144 knockdown on CRC progression was reversed by LARP1 over-expression. In conclusion, hsa_circRNA_002144 could sponge miR-615-5p to promote CRC progression through regulation of LARP1, providing a therapeutic target for cancer intervention.

scholarly journals The role of tumor angiogenesis as a therapeutic target in colorectal cancer

2018 ◽  
Vol 18 (3) ◽  
pp. 251-266 ◽  
Author(s):  
Francesca Battaglin ◽  
Alberto Puccini ◽  
Rossana Intini ◽  
Marta Schirripa ◽  
Alessandra Ferro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Angiogenesis ◽  
Therapeutic Target

scholarly journals TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 241
Author(s):  
Flaviana Marzano ◽  
Mariano Francesco Caratozzolo ◽  
Graziano Pesole ◽  
Elisabetta Sbisà ◽  
Apollonia Tullo
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
Therapeutic Target ◽  
Malignant Tumors ◽  
Premature Death ◽  
Chemotherapy Response ◽  
Protein Levels ◽  
Promising Therapeutic Target ◽  
Trim Proteins

Colorectal cancer (CRC) represents one of the most widespread forms of cancer in the population and, as all malignant tumors, often develops resistance to chemotherapies with consequent tumor growth and spreading leading to the patient’s premature death. For this reason, a great challenge is to identify new therapeutic targets, able to restore the drugs sensitivity of cancer cells. In this review, we discuss the role of TRIpartite Motifs (TRIM) proteins in cancers and in CRC chemoresistance, focusing on the tumor-suppressor role of TRIM8 protein in the reactivation of the CRC cells sensitivity to drugs currently used in the clinical practice. Since the restoration of TRIM8 protein levels in CRC cells recovers chemotherapy response, it may represent a new promising therapeutic target in the treatment of CRC.

scholarly journals Forkhead Box Q1 Is Critical to Angiogenesis and Macrophage Recruitment of Colorectal Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Hui Tang ◽  
Ji Zheng ◽  
Xuan Bai ◽  
Ke-Lin Yue ◽  
Jian-Hua Liang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Clinical Significance ◽  
Therapeutic Target ◽  
Essential Role ◽  
Multiple Tumors ◽  
Macrophage Recruitment ◽  
Forkhead Box

Angiogenesis and the tumor microenvironment (TME) play important roles in tumorigenesis. Forkhead box Q1 (FOXQ1) is a well-established oncogene in multiple tumors, including colorectal cancer (CRC); however, whether FOXQ1 contributes to angiogenesis and TME modification in CRC remains largely uncharacterized. Here, we demonstrate an essential role of FOXQ1-induced angiogenesis and macrophage recruitment in CRC that is related to its ability to promote the migration of endothelial cells and macrophages through activation of the EGF/PDGF pathway and the Twist1/CCL2 axis. We also provide evidence showing that the clinical significance between FOXQ1, Twist1, CCL2, and macrophage infiltration is associated with reduced 8-year survival in CRC patients. Our findings suggest FOXQ1 plays critical roles in the malignancy and progression of CRC, Therefore, FOXQ1 may serve as a therapeutic target for inhibiting angiogenesis and reducing macrophage recruitment in CRC.

scholarly journals RRAD expression in gastric and colorectal cancer with peritoneal carcinomatosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hee Kyung Kim ◽  
Inkyoung Lee ◽  
Seung Tae Kim ◽  
Jeeyun Lee ◽  
Kyoung-Mee Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Combined Treatment ◽  
Cancer Tissue ◽  
Associated Proteins ◽  
Emt Markers

AbstractThe role of Ras-related associated with diabetes (RRAD) in gastric cancer (GC) or colorectal cancer (CRC) has not been investigated. We aimed to investigate the biological and clinical roles of RRAD in GC and CRC and to assess RRAD as a therapeutic target. A total of 31 cancer cell lines (17 GC cell lines, 14 CRC cell lines), 59 patient-derived cells (PDCs from 48 GC patients and 11 CRC patients), and 84 matched pairs of primary cancer tissue and non-tumor tissue were used to evaluate the role of RRAD in vitro and in vivo. RRAD expression was frequently increased in GC and CRC cell lines, and siRNA/shRNA-mediated RRAD inhibition induced significant decline of tumor cell proliferation both in vitro and in vivo. A synergistic effect of RRAD inhibition was generated by combined treatment with chemotherapy. Notably, RRAD expression was markedly increased in PDCs, and RRAD inhibition suppressed PDC proliferation. RRAD inhibition also resulted in reduced cell invasion, decreased expression of EMT markers, and decreased angiogenesis and levels of associated proteins including VEGF and ANGP2. Our study suggests that RRAD could be a novel therapeutic target for treatment of GC and CRC, especially in patients with peritoneal seeding.

The Contemporary Role of Resection and Ablation in Colorectal Cancer Liver Metastases

2020 ◽  
Vol 04 (03) ◽  
pp. 291-302
Author(s):  
Mariam F. Eskander ◽  
Christopher T. Aquina ◽  
Aslam Ejaz ◽  
Timothy M. Pawlik
Keyword(s):  
Colorectal Cancer ◽  
Portal Vein ◽  
Surgical Oncology ◽  
Portal Vein Ligation ◽  
Safe Alternative ◽  
Colorectal Cancer Liver Metastases ◽  
Liver Remnant ◽  
New Era ◽  
Ablation Therapy

AbstractAdvances in the field of surgical oncology have turned metastatic colorectal cancer of the liver from a lethal disease to a chronic disease and have ushered in a new era of multimodal therapy for this challenging illness. A better understanding of tumor behavior and more effective systemic therapy have led to the increased use of neoadjuvant therapy. Surgical resection remains the gold standard for treatment but without the size, distribution, and margin restrictions of the past. Lesions are considered resectable if they can safely be removed with tumor-free margins and a sufficient liver remnant. Minimally invasive liver resections are a safe alternative to open surgery and may offer some advantages. Techniques such as portal vein embolization, association of liver partition with portal vein ligation for staged hepatectomy, and radioembolization can be used to grow the liver remnant and allow for resection. If resection is not possible, nonresectional ablation therapy, including radiofrequency and microwave ablation, can be performed alone or in conjunction with resection. This article presents the most up-to-date literature on resection and ablation, with a discussion of current controversies and future directions.

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