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Current Colorectal Cancer Reports

Carlyn Rose C Tan, Lanlan Zhou, Wafik S El-Deiry
Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials...
June 2016: Current Colorectal Cancer Reports
Ibrahim Nassour, Patricio M Polanco
Minimally invasive surgery has been cautiously introduced in surgical oncology over the last two decades due to a concern of compromised oncological outcomes. Recently, it has been adopted in liver surgery for colorectal metastases. Colorectal cancer is a major cause of cancer-related death in the USA. In addition, liver metastasis is the most common site of distant disease and its resection improves survival. While open resection was the standard of care, laparoscopic liver surgery has become the standard of care for minor liver resections...
April 2016: Current Colorectal Cancer Reports
Madeleine Young, Karen R Reed
Modelling human diseases in in vitro systems is undisputedly an invaluable research tool, yet there are many limitations. Some of those limitations have been overcome through the introduction of organoid culture systems, which have revolutionised colorectal cancer research and enabled an array of new experimental techniques. This 3D system models the physiology, shape, dynamics and cell make-up of the intestinal epithelium producing a relevant and highly adaptable model system. The increased functional relevance of this model compared to the use of 2D cancer cell lines makes it an invaluable tool for both basic and translational research...
2016: Current Colorectal Cancer Reports
Svetlana Balyasnikova, Gina Brown
The optimal management of rectal cancer is achieved through a shared multidisciplinary decision making process with accurate staging by imaging being critical for treatment planning. Good quality, high-resolution MRI has become the imaging gold standard as it allows consistent staging and stratification of patients into distinct prognostic groups according to MR-findings. Imaging features other than T and N have been proven to influence patient outcomes, and increasingly these features are taken into consideration when determining treatment options: distance of tumour to the potential circumferential margin (CRM), presence of tumour within the extramural rectal vessels (EMVI), discontinuous tumour deposits (N1c), relationship to the intersphincteric plane in low rectal tumours and to pelvic compartments in advanced disease...
2016: Current Colorectal Cancer Reports
Donna M Graham, Vicky M Coyle, Richard D Kennedy, Richard H Wilson
Development of colorectal cancer occurs via a number of key pathways, with the clinicopathological features of specific subgroups being driven by underlying molecular changes. Mutations in key genes within the network of signalling pathways have been identified; however, therapeutic strategies to target these aberrations remain limited. As understanding of the biology of colorectal cancer has improved, this has led to a move toward broader genomic testing, collaborative research and innovative, adaptive clinical trial design...
2016: Current Colorectal Cancer Reports
Christopher Coyle, Fay Helen Cafferty, Ruth Elizabeth Langley
There is now a considerable body of data supporting the hypothesis that aspirin could be effective in the prevention and treatment of colorectal cancer, and a number of phase III randomised controlled trials designed to evaluate the role of aspirin in the treatment of colorectal cancer are ongoing. Although generally well tolerated, aspirin can have adverse effects, including dyspepsia and, infrequently, bleeding. To ensure a favourable balance of benefits and risks from aspirin, a more personalised assessment of the advantages and disadvantages is required...
2016: Current Colorectal Cancer Reports
Kristen K Ciombor, Richard M Goldberg
Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen...
December 2015: Current Colorectal Cancer Reports
Elizabeth Hibler
Studies demonstrate that regular physical activity and, more recently, limited sedentary behavior are associated with reduced risk of colorectal neoplasia. However, the biological mechanisms of action for physical activity versus sedentary behavior are not clear. Epigenetic variation is suggested as a potential mechanism that would allow for independent, or possibly even synergistic, effects of activity and inactivity on colorectal epithelium. We describe the evidence for epigenetic variation as a link between physical activity and sedentary behavior in colorectal neoplasia risk...
December 2015: Current Colorectal Cancer Reports
Rahul Nayani, Hassan Ashktorab, Hassan Brim, Adeyinka O Laiyemo
African Americans suffer the highest burden from colorectal cancer (CRC) in the USA. Studies have suggested that healthcare access and poorer utilization of preventive services may be playing more of a role in this disparity. However, African Americans also tend to develop CRC at younger ages and are more likely to have proximal cancers. This raises the possibility of higher genetic predisposition to CRC among African Americans and this has not been well studied. In this article, we reviewed possible genetic basis underpinning biological differences in CRC burden in the USA...
December 1, 2015: Current Colorectal Cancer Reports
Timothy J Zumwalt, Ajay Goel
Patients with recurring or metastatic colorectal cancer (mCRC) have strikingly low long-term survival, while conventional treatments such as chemotherapeutic intervention and radiation therapy marginally improve longevity. Although, many factors involving immunosurveillance and immunosuppression were recently validated as important for patient prognosis and care, a multitude of experimental immunotherapies designed to combat unresectable mCRC have, in few cases, successfully mobilized antitumor immune cells against malignancies, nor conclusively or consistently granted protection, complete remission, and/or stable disease from immunotherapy - of which benefit less than 10% of those receiving therapy...
June 1, 2015: Current Colorectal Cancer Reports
Robin M J M van Geel, Jos H Beijnen, René Bernards, Jan H M Schellens
Colorectal cancer has been characterized as a genetically heterogeneous disease, with a large diversity in molecular pathogenesis resulting in differential responses to therapy. However, the currently available validated biomarkers KRAS, BRAF, and microsatellite instability do not sufficiently cover this extensive heterogeneity and are therefore not suitable to successfully guide personalized treatment. Recent studies have focused on novel targets and rationally designed combination strategies. Furthermore, a more comprehensive analysis of the underlying biology of the disease revealed distinct phenotypic differences within subgroups of patients harboring the same genetic driver mutation with both prognostic and predictive relevance...
2015: Current Colorectal Cancer Reports
Thomas J George, Carmen J Allegra, Greg Yothers
The conduct of clinical trials in colorectal cancer has historically relied upon endpoints such as disease-free (DFS) or overall survival (OS). While ideal, these endpoints require long-term follow-up, thus contributing to a slow pace of scientific progress in clinical research. Identification of short-term endpoints to serve as surrogates for DFS and OS would enable more rapid determination of success or failure of an experimental intervention and thus facilitate more scientific discovery and progress leading to clinical practice improvements...
2015: Current Colorectal Cancer Reports
Iris D Nagtegaal, Niek Hugen
Colorectal cancer is not just one type of cancer. Differences in outcome and reaction to treatment can at least be partly explained by different histological and molecular subtypes. Recognition of these differences may influence treatment decisions. However, there is huge variation in the amount of information that is available. Several tumour types such as mucinous carcinoma, signet ring cell carcinoma, neuroendocrine carcinoma and adenosquamous carcinoma have such a distinct phenotype that they are readily recognised...
2015: Current Colorectal Cancer Reports
Alicia Garcia-Anguita, Artemisia Kakourou, Konstantinos K Tsilidis
A substantial number of prospective epidemiological studies have been conducted to investigate the association between biomarkers of inflammation and immune function and risk of colorectal cancer. Although pre-diagnostic concentrations of these biomarkers, especially C-reactive protein, have been associated with a higher risk of colorectal cancer in some studies, this association does not seem to have a robust support without hints of bias. Future prospective studies should evaluate multiple inflammatory biomarkers with longitudinal measures over the follow-up taking advantage of new multiplex cytokine quantification arrays and use more sophisticated joint or biomarker pattern statistical approaches to capture the complex and dynamic interplay between biomarkers and risk of colorectal cancer...
2015: Current Colorectal Cancer Reports
Tina Yen-Ting Chen, Katrine J Emmertsen, Søren Laurberg
With enhanced surgical techniques and neoadjuvant therapy in rectal cancer, survivorship issues are at the forefront of clinical practice and research. More and more patients are living with altered bowel habits following rectal cancer surgery. Sound assessment of anorectal function after rectal cancer surgery is the foundation for the continuing effort to explore the adverse effects of such surgery on bowel function, as well as for working towards reducing these effects. The quality of the assessment is predominantly determined by the instrument administered...
2015: Current Colorectal Cancer Reports
Hassan Ashktorab, Hassan Brim
Colorectal cancer (CRC) is one of the major cancers in the world and second death-causing cancer in the US. CRC development involves genetic and epigenetic alterations. Changes in DNA methylation status are believed to be involved at different stages of CRC. Promoter silencing via DNA methylation and hypomethylation of oncogenes alter genes' expression, and can be used as a tool for the early detection of colonic lesions. DNA methylation use as diagnostic and prognostic marker has been described for many cancers including CRC...
December 1, 2014: Current Colorectal Cancer Reports
Santanu Paul, Satish Ramalingam, Dharmalingam Subramaniam, Joaquina Baranda, Shrikant Anant, Animesh Dhar
Cell growth and proliferation are controlled through different posttranslational modifications including demethylation, a process regulated by regulated by the demethylase enzymes. This review focuses on our current understanding of functional and therapeutic potentials of histone demethylases in colon cancer. Colon cancer is the third most common malignancy worldwide and the second leading cause of cancer deaths in the United States. The key protein families responsible for demethylation of histones, histone demethylases, have emerged as new therapeutic targets in different cancer types including colon cancer...
December 1, 2014: Current Colorectal Cancer Reports
Robert S Chapkin, Vanessa DeClercq, Eunjoo Kim, Natividad Roberto Fuentes, Yang-Yi Fan
Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. Genetic susceptibility and diet are primary determinants of cancer risk and tumor behavior. Experimental, epidemiological, and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFA) in preventing chronic inflammation and colon cancer. From a mechanistic perspective, n-3 PUFA are pleiotropic and multifaceted with respect to their molecular mechanisms of action. For example, this class of dietary lipid uniquely alters membrane structure/ cytoskeletal function, impacting membrane receptor function and downstream signaling cascades, including gene expression profiles and cell phenotype...
December 1, 2014: Current Colorectal Cancer Reports
Suman Suman, Trinath P Das, Murali K Ankem, Chendil Damodaran
The activation of Notch signaling is implicated in tumorigenesis in the colon due to the induction of pro-survival signaling in colonic epithelial cells. Chemoresistance is a major obstacle for treatment and for the complete eradication of colorectal cancer (CRC), hence, the inhibition of Notch is an attractive target for CRC and several groups are working to identify small molecules or monoclonal antibodies that inhibit Notch or its downstream events; however, toxicity profiles in normal cells and organs often impede the clinical translation of these molecules...
December 1, 2014: Current Colorectal Cancer Reports
Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Next generation sequencing methods have exponentially increased the amount of genomic information available to scientists and clinicians. This review will explain the evolution of tumor gene sequencing and identify its potential to accelerate therapeutic progress by using colorectal cancer to illustrate the benefits of this type of analysis. A milestone in sequencing occurred when The Cancer Genome Atlas investigators characterized the genomes of 276 colorectal cancer samples, with the resulting information expected to provide future clinical applications and help to guide the treatment of colorectal cancer...
December 1, 2014: Current Colorectal Cancer Reports
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