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Current Colorectal Cancer Reports

Emma M Schatoff, Benjamin I Leach, Lukas E Dow
The WNT signaling pathway is a critical mediator of tissue homeostasis and repair, and frequently co-opted during tumor development. Almost all colorectal cancers (CRC) demonstrate hyperactivation of the WNT pathway, which in many cases is believed to be the initiating and driving event. In this short review, we provide a focused overview of recent developments in our understanding of the WNT pathway in CRC, describe new research tools that are enabling a deeper understanding of WNT biology, and outline ongoing efforts to target this pathway therapeutically...
April 2017: Current Colorectal Cancer Reports
John M Carethers
Microsatellite instability (MSI) refers to the biochemical detection of frameshifted microsatellite sequences from genomic DNA. Genesis of MSI is due to defective DNA mismatch repair (MMR) that fails to correct post DNA replicative slippage mistakes at microsatellites. Most of the estimated 100,000 genomic microsatellites are non-coding; however, ~150-300 microsatellites are coding such that, when frameshifted during the pathogenesis of an MSI tumor, can generate immunogenic neopeptide antigens that limit the growth of tumor and prolong patient survival...
February 2017: Current Colorectal Cancer Reports
Upender Manne, Trafina Jadhav, Balananda-Dhurjati Kumar Putcha, Temesgen Samuel, Shivani Soni, Chandrakumar Shanmugam, Esther A Suswam
This review provides updates on the efforts for the development of prognostic and predictive markers in colorectal cancer based on the race/ethnicity of patients. Since the clinical consequences of genetic and molecular alterations differ with patient race and ethnicity, the usefulness of these molecular alterations as biomarkers needs to be evaluated in different racial/ethnic groups. To accomplish personalized patient care, a combined analysis of multiple molecular alterations in DNA, RNA, microRNAs (miRNAs), metabolites, and proteins in a single test is required to assess disease status in a precise way...
December 2016: 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
Motaz Qadan, Michael I D'Angelica
Colorectal cancer is the third most common malignancy in the USA and continues to pose a significant epidemiologic problem, despite major advances in the treatment of patients with advanced disease. Up to 50 % of patients will develop metastatic disease at some point during the course of their disease, with the liver being the most common site of metastatic disease. In this review, we address the relatively poorly defined entity of borderline-resectable colorectal liver metastases. The workup and staging of borderline-resectable disease are discussed...
December 2015: 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
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