scholarly journals Genomic Alterations and Their Implications on Survival in Nonmetastatic Colorectal Cancer: Status Quo and Future Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2001 ◽  
Author(s):  
Reetu Mukherji ◽  
John Marshall ◽  
Andreas Seeber
Keyword(s):  
Colorectal Cancer ◽  
Current Knowledge ◽  
Locally Advanced ◽  
Tumor Resection ◽  
Daily Routine ◽  
Precision Oncology ◽  
Genomic Alterations ◽  
Future Challenges ◽  
The Status ◽  
Selection Of

The selection of treatment according to genomic alterations is a standard approach in metastatic colorectal cancer but is only starting to have an impact in the earlier stages of the disease. The status of genes like KRAS, BRAF, and MMR has substantial survival implications, and concerted research efforts have revolutionized treatment towards precision oncology. In contrast, a genomic-based approach has not changed the adjuvant setting after curative tumor-resection in the daily routine so far. This review focuses on the current knowledge regarding prognostic and predictive genomic biomarkers in patients with locally advanced nonmetastasized colorectal cancer. Furthermore, we provide an outlook on future challenges for a personalized adjuvant treatment approach in patients with colorectal cancer.

scholarly journals TCox: Correlation-Based Regularization Applied to Colorectal Cancer Survival Data

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 488
Author(s):  
Carolina Peixoto ◽  
Marta B. Lopes ◽  
Marta Martins ◽  
Luís Costa ◽  
Susana Vinga
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gene Expression Data ◽  
Survival Data ◽  
Significant Risk ◽  
Survival Models ◽  
Precision Oncology ◽  
Expression Data ◽  
Network Information ◽  
Selection Of

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Being a heterogeneous disease, cancer therapy and prognosis represent a significant challenge to medical care. The molecular information improves the accuracy with which patients are classified and treated since similar pathologies may show different clinical outcomes and other responses to treatment. However, the high dimensionality of gene expression data makes the selection of novel genes a problematic task. We propose TCox, a novel penalization function for Cox models, which promotes the selection of genes that have distinct correlation patterns in normal vs. tumor tissues. We compare TCox to other regularized survival models, Elastic Net, HubCox, and OrphanCox. Gene expression and clinical data of CRC and normal (TCGA) patients are used for model evaluation. Each model is tested 100 times. Within a specific run, eighteen of the features selected by TCox are also selected by the other survival regression models tested, therefore undoubtedly being crucial players in the survival of colorectal cancer patients. Moreover, the TCox model exclusively selects genes able to categorize patients into significant risk groups. Our work demonstrates the ability of the proposed weighted regularizer TCox to disclose novel molecular drivers in CRC survival by accounting for correlation-based network information from both tumor and normal tissue. The results presented support the relevance of network information for biomarker identification in high-dimensional gene expression data and foster new directions for the development of network-based feature selection methods in precision oncology.

scholarly journals Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Aitor Rodriguez-Casanova ◽  
Nicolás Costa-Fraga ◽  
Aida Bao-Caamano ◽  
Rafael López-López ◽  
Laura Muinelo-Romay ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Monitoring And Evaluation ◽  
Precision Oncology ◽  
Epigenetic Mechanisms ◽  
Epigenetic Alterations ◽  
Liquid Biopsies ◽  
Dna And Rna

Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.

18F-Fluorodeoxyglucose positron emission tomography in restaging of colorectal cancer

2003 ◽  
Vol 42 (04) ◽  
pp. 145-156 ◽  
Author(s):  
W. Weber ◽  
M. Schwaiger ◽  
H. Schicha ◽  
M. Dietlein
Keyword(s):  
Colorectal Cancer ◽  
Fdg Pet ◽  
Classification Systems ◽  
Correct Selection ◽  
Daily Routine ◽  
Health Administration ◽  
Clinical Implementation ◽  
Level Of Evidence ◽  
Selection Of Patients ◽  
Selection Of

Summary: Aim, method: Recommendations for the use of FDG-PET in relapsed colorectal cancer and the decision of reimbursement should base on published studies and on their level of evidence. Therefore, the PET-studies published between 1997 and 2002 were graded by the bias-criteria, by two rating-systems and by two classification-systems for the level of evidence according to AHCPR (Agency for Health Care Policy and Research) and VHA (Veterans Health Administration). Results: The recommendation for the use of PET in relapsed colorectal cancer reached the level IIa according to the AHCPR, corresponding to level B according to the VHA. The sensitivity and specificity of FDG-PET were 94% (95% CI: 91-96%) and 78% (95% CI: 69-86%), respectively. Staging was changed correctly in 27% of patients (95% CI: 24-30%). Staging by FDG-PET was incorrect in 4% of the patients (95% CI: 2-5%) compared with the conventionel methods. The additional use of PET changed the prospectively defined management plan for 34% of patients (95% CI: 31-38%). Either potentially curative operations were initiated in case of resectable tumour or futile operations were cancelled in case of multiple metastases. Conclusion: The 3-year-survival-rate following surgery would have exceeded 70% if the selection of patients had included an additional PET-examination. The correct selection of patients is requested in the daily routine as well as in the clinical implementation of neoadjuvant therapies to prevent a selection-bias from a suboptimal restaging without PET.

scholarly journals The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Beatriz Subtil ◽  
Alessandra Cambi ◽  
Daniele V. F. Tauriello ◽  
I. Jolanda M. de Vries
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Critical Role ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Future Research ◽  
The Impact

Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-related deaths worldwide. Locally advanced and metastatic disease exhibit resistance to therapy and are prone to recurrence. Despite significant advances in standard of care and targeted (immuno)therapies, the treatment effects in metastatic CRC patients have been modest. Untreatable cancer metastasis accounts for poor prognosis and most CRC deaths. The generation of a strong immunosuppressive tumor microenvironment (TME) by CRC constitutes a major hurdle for tumor clearance by the immune system. Dendritic cells (DCs), often impaired in the TME, play a critical role in the initiation and amplification of anti-tumor immune responses. Evidence suggests that tumor-mediated DC dysfunction is decisive for tumor growth and metastasis initiation, as well as for the success of immunotherapies. Unravelling and understanding the complex crosstalk between CRC and DCs holds promise for identifying key mechanisms involved in tumor progression and spread that can be exploited for therapy. The main goal of this review is to provide an overview of the current knowledge on the impact of CRC-driven immunosuppression on DCs phenotype and functionality, and its significance for disease progression, patient prognosis, and treatment response. Moreover, present knowledge gaps will be highlighted as promising opportunities to further understand and therapeutically target DC dysfunction in CRC. Given the complexity and heterogeneity of CRC, future research will benefit from the use of patient-derived material and the development of in vitro organoid-based co-culture systems to model and study DCs within the CRC TME.

scholarly journals The Landscape of Actionable Gene Fusions in Colorectal Cancer

2019 ◽  
Vol 20 (21) ◽  
pp. 5319 ◽  
Author(s):  
Filippo Pagani ◽  
Giovanni Randon ◽  
Vincenzo Guarini ◽  
Alessandra Raimondi ◽  
Michele Prisciandaro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Current Knowledge ◽  
Gene Fusions ◽  
Wild Type ◽  
Kinase Gene ◽  
Treatment Scenario ◽  
Remarkable Improvement ◽  
Novel Therapeutic Strategies ◽  
Basket Trials ◽  
Selection Of

The treatment scenario of metastatic colorectal cancer (mCRC) has been rapidly enriched with new chemotherapy combinations and biological agents that lead to a remarkable improvement in patients’ outcome. Kinase gene fusions account for less than 1% of mCRC overall but are enriched in patients with high microsatellite instability, RAS/BRAF wild-type colorectal cancer. mCRC patients harboring such alterations show a poor prognosis with standard treatments that could be reversed by adopting novel therapeutic strategies. Moving forward to a positive selection of mCRC patients suitable for targeted therapy in the era of personalized medicine, actionable gene fusions, although rare, represent a peculiar opportunity to disrupt a tumor alteration to achieve therapeutic goal. Here we summarize the current knowledge on potentially actionable gene fusions in colorectal cancer available from retrospective experiences and promising preliminary results of new basket trials.

scholarly journals Proof-of-concept pilot study on comprehensive spatiotemporal intra-patient heterogeneity for colorectal cancer with liver metastasis

2021 ◽  
Author(s):  
Ioannis Dimitrios Kyrochristos ◽  
Georgios K. Glantzounis ◽  
Anna Goussia ◽  
Alexia Eliades ◽  
Achilleas Achilleos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
De Novo ◽  
Tumor Resection ◽  
Tumor Evolution ◽  
Precision Oncology ◽  
Proof Of Concept ◽  
De Novo Mutations ◽  
Liquid Biopsies ◽  
Patient Heterogeneity

Purpose: The mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) and liver metastasis (LM) remain poorly understood. We evaluate the potential translational implications of intra-patient heterogeneity (IPH) comprising primary and matched metastatic intratumor heterogeneity (ITH) coupled with circulating tumor DNA (ctDNA) variability. Patients and methods: According to our IPH-based protocol, 18 eligible patients with CRC-LM, who underwent complete tumor resection after neo-adjuvant treatment, with a total of 122 multi-regional tumor and perioperative liquid biopsies were analyzed via next-generation sequencing (NGS) of a custom 77-gene panel. The primary endpoints were the extent of IPH and the frequency of actionable mutations. Results: The proportion of patients with ITH were 53% and 56% in primary CRC and LM respectively, while 35% of patients harbored de novo mutations in LM indicating spatiotemporal tumor evolution and the necessity of multiregional analysis. Among the 56% of patients with alterations in liquid biopsies, de novo mutations in cfDNA were identified in 25% of patients, which were undetectable in both CRC and LM. All 17 patients with driver alterations harbored actionable mutations, with an average of 3.2 oncogenic events per patient, for molecularly targeted drugs either approved or under evaluation in ongoing clinical trials or in pre-clinical studies. Conclusions: Our proof-of-concept prospective study provides initial evidence and warrants the conduction of precision oncology trials to test the potential clinical utility of IPH-driven matched therapy.

Bibliography of publications written by Alwyne (Wyn) Cooper Wheeler (1929–2005)

2009 ◽  
Vol 36 (1) ◽  
pp. 77-99 ◽  
Author(s):  
ANN DATTA
Keyword(s):  
Fish Fauna ◽  
Archaeological Sites ◽  
Changing Environment ◽  
Scientific Papers ◽  
The Status ◽  
Fish Remains ◽  
Important Fish ◽  
Selection Of

The bibliography brings together more than 250 scientific papers and books written by Alwyne (Wyn) Wheeler over fifty years, from 1955–2006. This chronological list shows that from the beginning his research followed three themes: taxonomy of historically important fish collections; identification and distribution of the British and European fish fauna ; the status of British fishes in a changing environment. Until the mid-point in Wyn's career he published regularly on the identification of fish remains in archaeological sites in Britain and Europe. Wyn also wrote under an alias, Allan Cooper, and these have been listed separately. The bibliography concludes with a selection of the regular columns he contributed to angling magazines.

The Selection of Children's Books Translated from Spanish to Galician, Basque and Catalan (1940–80)

2009 ◽  
Vol 2 (2) ◽  
pp. 243-258
Author(s):  
Mónica Domínguez Pérez
Keyword(s):  
Social Economic ◽  
Children’S Literature ◽  
Status Quo ◽  
Intercultural Relations ◽  
Children's Books ◽  
Source Text ◽  
The Status ◽  
Castilian Spanish ◽  
Different Levels ◽  
Selection Of

This study deals with children's literature translated from Castilian Spanish into Galician, Basque and Catalan by a different publisher from that of the source text, between 1940 and 1980, and with the criteria used to choose books for translation during that period. It compares the different literatures within Spain and examines the intersystemic and intercultural relations that the translations reflect. Following the polysystems theory, literature is here conceived as a network of agents of different kinds: authors, publishers, readers, and literary models. Such a network, called a polysystem, is part of a larger social, economic, and cultural network. These extra-literary considerations play an important role in determining the selection of works to be translated. The article suggests that translations can be said to establish transcultural relations, and that they demonstrate different levels of power within a specific interliterary community. It concludes that, while translations may aim to change the pre-existent relationships, frequently they just reflect the status quo.

EXPERIENCE OF THE APPLICATION OF THERMOCHEMIORRADIOTHERAPY IN COMBINED TREATMENT OF DYSTAL CANCER OF DIRECT INTESTINE

2019 ◽  
Vol 65 (1) ◽  
pp. 131-134
Author(s):  
Zhanna Startseva ◽  
Sergey Afanasev ◽  
Dina Plaskeeva
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Primary Tumor ◽  
Advanced Colorectal Cancer ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Chemoradiation Therapy ◽  
Locally Advanced Colorectal Cancer

The article describes the experience of using ther-mochioradiotherapy in the combined treatment of distal locally advanced colorectal cancer, as well as comparing the effectiveness of treatment with chemoradiation therapy. The use of the proposed method as a component of the combined treatment of patients with rectal cancer allowed to increase the percentage of organ-preserving operations. As a result of thermochemotherapy, the prevalence of the primary tumor was significantly reduced, as a result of which the number of sphincter-bearing operations was reduced by almost 2 times (p

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