Therapeutic Approaches Targeting the Serrated Pathway of Colorectal Cancer Characterized by Mutation in the BRAF Gene and Overexpression of GTPase Rac1b

2017 ◽  
pp. 233-255
Author(s):  
Paulo Matos ◽  
Vânia Gonçalves ◽  
Peter Jordan
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Approaches ◽  
Braf Gene ◽  
Serrated Pathway

scholarly journals LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 195
Author(s):  
Francisca Dias ◽  
Cristina Almeida ◽  
Ana Luísa Teixeira ◽  
Mariana Morais ◽  
Rui Medeiros
Keyword(s):  
Colorectal Cancer ◽  
Amino Acid ◽  
Cancer Progression ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Amino Acid Transporters ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Colorectal Cancer Progression ◽  
Made In

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

scholarly journals Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ke-Tao Jin ◽  
Bo Chen ◽  
Yu-Yao Liu ◽  
H uan-Rong Lan ◽  
Jie-Ping Yan
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Monoclonal Antibodies ◽  
Immune Responses ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Therapeutic Approaches ◽  
Great Ability ◽  
Car T Cells ◽  
Car T

AbstractColorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.

scholarly journals The Pivotal Player: Components of NF-κB Pathway as Promising Biomarkers in Colorectal Cancer

2021 ◽  
Vol 22 (14) ◽  
pp. 7429
Author(s):  
Matthew Martin ◽  
Mengyao Sun ◽  
Aishat Motolani ◽  
Tao Lu
Keyword(s):  
Colorectal Cancer ◽  
Biological Response ◽  
Significant Progress ◽  
Therapeutic Approaches ◽  
Successful Development ◽  
Diagnostic Screening ◽  
Proteomic Data ◽  
Large Groups ◽  
Made In

Over the last several decades, colorectal cancer (CRC) has been one of the most prevalent cancers. While significant progress has been made in both diagnostic screening and therapeutic approaches, a large knowledge gap still remains regarding the early identification and treatment of CRC. Specifically, identification of CRC biomarkers that can help with the creation of targeted therapies as well as increasing the ability for clinicians to predict the biological response of a patient to therapeutics, is of particular importance. This review provides an overview of CRC and its progression stages, as well as the basic types of CRC biomarkers. We then lay out the synopsis of signaling pathways related to CRC, and further highlight the pivotal and multifaceted role of nuclear factor (NF) κB signaling in CRC. Particularly, we bring forth knowledge regarding the tumor microenvironment (TME) in CRC, and its complex interaction with cancer cells. We also provide examples of NF-κB signaling-related CRC biomarkers, and ongoing efforts made at targeting NF-κB signaling in CRC treatment. We conclude and anticipate that with more emerging novel regulators of the NF-κB pathway being discovered, together with their in-depth characterization and the integration of large groups of genomic, transcriptomic and proteomic data, the day of successful development of more ideal NF-κB inhibitors is fast approaching.

scholarly journals Sa1163 Modelling the Adenoma and Serrated Pathway to Colorectal Cancer (ASCCA)

2013 ◽  
Vol 144 (5) ◽  
pp. S-218
Author(s):  
Marjolein J. Greuter ◽  
Xiang-Ming Xu ◽  
Jie-Bin Lew ◽  
Evelien Dekker ◽  
Ernst J. Kuipers ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Serrated Pathway

Receptor tyrosine kinase fusions act as a significant alternative driver of the serrated pathway in colorectal cancer development

2020 ◽  
Vol 251 (1) ◽  
pp. 74-86 ◽  
Author(s):  
Anthony W‐H Chan ◽  
Yi Pan ◽  
Joanna H‐M Tong ◽  
Raymond W‐M Lung ◽  
Johnny S‐H Kwan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Cancer Development ◽  
Serrated Pathway

scholarly journals MicroRNA-146a limits tumorigenic inflammation in colorectal cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lucien P. Garo ◽  
Amrendra K. Ajay ◽  
Mai Fujiwara ◽  
Galina Gabriely ◽  
Radhika Raheja ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Development ◽  
Myeloid Cell ◽  
Negative Regulator ◽  
Sporadic Colorectal Cancer ◽  
Intestinal Epithelial ◽  
Therapeutic Approaches ◽  
Colonic Inflammation ◽  
Small Molecule Inhibition ◽  
Deficient Mice

AbstractChronic inflammation can drive tumor development. Here, we have identified microRNA-146a (miR-146a) as a major negative regulator of colonic inflammation and associated tumorigenesis by modulating IL-17 responses. MiR-146a-deficient mice are susceptible to both colitis-associated and sporadic colorectal cancer (CRC), presenting with enhanced tumorigenic IL-17 signaling. Within myeloid cells, miR-146a targets RIPK2, a NOD2 signaling intermediate, to limit myeloid cell-derived IL-17-inducing cytokines and restrict colonic IL-17. Accordingly, myeloid-specific miR-146a deletion promotes CRC. Moreover, within intestinal epithelial cells (IECs), miR-146a targets TRAF6, an IL-17R signaling intermediate, to restrict IEC responsiveness to IL-17. MiR-146a within IECs further suppresses CRC by targeting PTGES2, a PGE2 synthesis enzyme. IEC-specific miR-146a deletion therefore promotes CRC. Importantly, preclinical administration of miR-146a mimic, or small molecule inhibition of the miR-146a targets, TRAF6 and RIPK2, ameliorates colonic inflammation and CRC. MiR-146a overexpression or miR-146a target inhibition represent therapeutic approaches that limit pathways converging on tumorigenic IL-17 signaling in CRC.

scholarly journals Evaluation and identification of factors related to KRAS and BRAF gene mutations in colorectal cancer: A meta-analysis

2016 ◽  
Vol 12 (7) ◽  
pp. 191 ◽  
Author(s):  
Mei-yu Fang ◽  
Li Lin ◽  
Guang-yong Chen ◽  
Chun-wei Xu ◽  
Hai-yan Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Gene Mutations ◽  
Braf Gene

scholarly journals DNA methylation-based signature of CD8+ tumor-infiltrating lymphocytes enables evaluation of immune response and prognosis in colorectal cancer

2021 ◽  
Vol 9 (9) ◽  
pp. e002671
Author(s):  
Qi Zou ◽  
Xiaolin Wang ◽  
Donglin Ren ◽  
Bang Hu ◽  
Guannan Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Immune Response ◽  
T Cell ◽  
Strong Association ◽  
Tumor Infiltrating Lymphocytes ◽  
Cd8 T Cell ◽  
Therapeutic Approaches ◽  
Single Base Resolution ◽  
Infiltrating Lymphocytes

BackgroundTumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC).MethodsA CD8+ MeTIL signature score was constructed by using CD8+ T cell-specific differentially methylated positions (DMPs) that were identified from Illumina EPIC methylation arrays. Immune cells, colon epithelial cells, and two CRC cohorts (n=282 and 335) were used to develop a PCR-based assay for quantitative analysis of DNA methylation at single-base resolution (QASM) to determine CD8 + MeTIL signature score.ResultsThree CD8+ T cell-specific DMPs were identified to construct the CD8+ MeTIL signature score, which showed a dramatic discriminability between CD8+ T cells and other cells. The QASM assay we developed for CD8+ MeTIL markers could measure CD8+ TILs distributions in a fully quantitative, accurate, and simple manner. The CD8+ MeTIL score determined by QASM assay showed a strong association with histopathology-based CD8+ TIL counts and a gene expression-based immune marker. Furthermore, the low CD8+ MeTIL score (enriched CD8+ TILs) was associated with MSI-H tumors and predicted better survival in CRC cohorts.ConclusionsThis study developed a quantitative DNA methylation-based signature that was reliable to evaluate CD8+ TILs and prognosis in CRC. This approach has the potential to be a tool for investigations on CD8+ TILs and a biomarker for therapeutic approaches, including immunotherapy.

scholarly journals Molecular Pathogenesis of Colorectal Cancer with an Emphasis on Recent Advances in Biomarkers, as Well as Nanotechnology-Based Diagnostic and Therapeutic Approaches

Nanomaterials ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 169
Author(s):  
Fakhria A. Al-Joufi ◽  
Aseem Setia ◽  
Mounir M. Salem-Bekhit ◽  
Ram Kumar Sahu ◽  
Fulwah Y. Alqahtani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Conceptual Knowledge ◽  
Water Solubility ◽  
Diagnostic Techniques ◽  
Molecular Pathogenesis ◽  
Colorectal Adenomas ◽  
Screening Methods ◽  
Therapeutic Approaches ◽  
Early Cancer Diagnosis

Colorectal cancer (CRC) is a serious disease that affects millions of people throughout the world, despite considerable advances in therapy. The formation of colorectal adenomas and invasive adenocarcinomas is the consequence of a succession of genetic and epigenetic changes in the normal colonic epithelium. Genetic and epigenetic processes associated with the onset, development, and metastasis of sporadic CRC have been studied in depth, resulting in identifying biomarkers that might be used to predict behaviour and prognosis beyond staging and influence therapeutic options. A novel biomarker, or a group of biomarkers, must be discovered in order to build an accurate and clinically useful test that may be used as an alternative to conventional methods for the early detection of CRC and to identify prospective new therapeutic intervention targets. To minimise the mortality burden of colorectal cancer, new screening methods with higher accuracy and nano-based diagnostic precision are needed. Cytotoxic medication has negative side effects and is restricted by medication resistance. One of the most promising cancer treatment techniques is the use of nano-based carrier system as a medication delivery mechanism. To deliver cytotoxic medicines, targeted nanoparticles might take advantage of differently expressed molecules on the surface of cancer cells. The use of different compounds as ligands on the surface of nanoparticles to interact with cancer cells, enabling the efficient delivery of antitumor medicines. Formulations based on nanoparticles might aid in early cancer diagnosis and help to overcome the limitations of traditional treatments, including low water solubility, nonspecific biodistribution, and restricted bioavailability. This article addresses about the molecular pathogenesis of CRC and highlights about biomarkers. It also provides conceptual knowledge of nanotechnology-based diagnostic techniques and therapeutic approaches for malignant colorectal cancer.

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