scholarly journals Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy

2013 ◽  
Vol 14 (1) ◽  
pp. 14-19 ◽  
Author(s):  
F V Negri ◽  
A Musolino ◽  
N Naldi ◽  
B Bortesi ◽  
G Missale ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immunoglobulin G ◽  
Cellular Cytotoxicity ◽  
Cetuximab Therapy ◽  
Receptor Polymorphism

scholarly journals Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Huashan Liu ◽  
Zhenxing Liang ◽  
Chi Zhou ◽  
Ziwei Zeng ◽  
Fengwei Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Biological Functions ◽  
Tumor Associated Macrophages ◽  
Defense Strategies ◽  
A Cell ◽  
Cetuximab Therapy

AbstractOncogenic KRAS has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer (CRC). Here, we demonstrate a cell-extrinsic role of KRAS, where KRAS engages with the tumor microenvironment by functional reprogramming of tumor-associated macrophages (TAMs). In human CRC specimens, mutant KRAS positively correlates with the presence of TAMs. Mutationally activated KRAS in tumor cells reprograms macrophages to a TAM-like phenotype via a combination effect of tumor-derived CSF2 and lactate. In turn, KRAS-reprogrammed macrophages were shown to not only promote tumor progression but also induce the resistance of tumor cells to cetuximab therapy. Mechanistically, KRAS drives the production of CSF2 and lactate in tumor cells by stabilizing hypoxia-inducible factor-1α (HIF-1α), a transcription factor that controls the expression of CSF2 and glycolytic genes. Mutant KRAS increased the production of reactive oxygen species, an inhibitor of prolyl hydroxylase activity which decreases HIF-1α hydroxylation, leading to enhanced HIF-1α stabilization. This cell-extrinsic mechanism awards KRAS a critical role in engineering a permissive microenvironment to promote tumor malignancy, and may present new insights on potential therapeutic defense strategies against mutant KRAS tumors.

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.

The Critical Role of the miR-21-MEG2 Axis in Colorectal Cancer

2020 ◽  
Vol 30 (6) ◽  
pp. 509-518
Author(s):  
Zengtao Bao ◽  
Shanting Gao ◽  
Baoming Zhang ◽  
Wenchao Shi ◽  
Aimin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Critical Role

THE ROLE OF RADIATION METHODS IN DIAGNOSIS AND STAGING OF COLORECTAL CANCER

2018 ◽  
pp. 93-102
Author(s):  
V. A. Solodkiy ◽  
N. V. Nudnov ◽  
V. D. Chhikvadze ◽  
U. S. Stanojevich ◽  
N. I. Sergeev ◽  
...  
Keyword(s):  
Colorectal Cancer

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

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.

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