Histone Demethylases in Colon Cancer
Abstract
Cell growth and proliferation are controlled through different posttranslational modifications including demethylation, a process 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 USA. The key protein families responsible for demethylation of histones, histone demethylases, have emerged as new therapeutic targets in different cancer types including colon cancer. These f...
Source: Current Colorectal Cancer Reports - September 30, 2014 Category: Cancer & Oncology Source Type: research
Targeting Notch Signaling in Colorectal Cancer
Abstract
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. Dietary agents have gained momentu...
Source: Current Colorectal Cancer Reports - September 21, 2014 Category: Cancer & Oncology Source Type: research
Peptide Vaccines for Treatment of Colon Cancer: Have We Made Progress?
Abstract
Colorectal cancer (CRC) is the third most common cancer diagnosis and cause of cancer-related death in the USA. It accounts for more than one million cases diagnosed each year worldwide. In the past 10 years, new drugs have been approved, but the survival times are still modest. Alternative therapeutic strategies are clearly needed. A large number of tumor antigens and epitopes recognized by cytotoxic T lymphocytes (CTLs) have been identified in CRC. Cancer vaccines, designed to activate immune effectors (T cells and antibodies), to prevent recurrence, or to treat advanced cancers, have demonstr...
Source: Current Colorectal Cancer Reports - September 17, 2014 Category: Cancer & Oncology Source Type: research
Adoptive Cell Therapy for Colon Cancer: the Right Choice?
Abstract
Despite significant advances in the treatment and prognosis of colorectal cancer (CRC), not all tumors respond to current treatment modalities and patients with advanced disease continue to have a poor prognosis. New treatment strategies are needed to improve long-term survival in colorectal cancer patients with metastatic disease. Adoptive cell therapy is a novel approach that uses one’s own immune cells to target tumor cells directly. For the last two decades, a wide variety of methods have been described. T-lymphocyte-based immunotherapy may be a promising alternative treatment capable of me...
Source: Current Colorectal Cancer Reports - September 9, 2014 Category: Cancer & Oncology Source Type: research
Role of Prolactin and Its Receptor in Colorectal Cancer
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the USA. Worldwide, up to 5 % of all reported cancer cases are due to CRC, with ∼60 % occurring in industrially developed or developing countries. Environmental factors ranging from changing dietary habits to environmental toxins are associated with the development of CRC. Germline mutations in APC, TP53, and DNA mismatch repair genes contribute to nearly 35 % of the registered CRC cases and are by far the best-studied factors for CRC. Hormones are critical regulatory factors produced by the body to regulate diver...
Source: Current Colorectal Cancer Reports - September 7, 2014 Category: Cancer & Oncology Source Type: research
New Targets and New Drug Development in Colorectal Cancer
Abstract
Despite improvements in clinical outcomes of patients with colorectal cancer (CRC) over the past decades, prognosis remains poor, with a 5-year survival rate of less than 10 %. Fluoropyrimidine-based regimens have defined the standard of care for metastatic disease. However, with the identification of different genetic alterations involved in tumor cell signaling pathways, understanding the molecular pathogenesis of CRC has become of increasing importance in order to select personalized targeted therapies from which patients may potentially benefit. RAS mutations have proven to predict respons...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Clinical End Points and Relevant Clinical Benefits in Advanced Colorectal Cancer Trials
Discussion of which variable represents the benefits derived from the adoption of a new treatment in a more reliable manner is of vital importance, both for the design of future clinical trials and for the interpretation of their results, and also to transfer them satisfactorily into clinical practice. Overall survival remains the end point which reflects the clinical benefit most clearly, followed by quality of life and patients’ reported outcomes. However, it may not always be feasible to choose overall survival as the primary end point. Must progression-free survival or other surrogate end points replace overall survi...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Oxaliplatin Neurotoxicity
Abstract
Oxaliplatin (OXA) is a first-line agent in the systemic treatment of colorectal cancer (CRC). OXA-induced neuropathy is the most prominent adverse effect, both during and after the completion of chemotherapy. OXA neurotoxicity (OXA-NTX) is a dose-limiting, frequent, and long-lasting adverse event that may compromise therapeutic outcome and the quality-of-life of CRC patients. Increased knowledge of the pathophysiology and clinical profile of this neuropathy is being achieved. Two types of neuropathy are usually observed, and evidence suggests a link between the acute symptoms and the developmen...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Optimization of Anti-EGFR Treatment of Advanced Colorectal Cancer
Abstract
Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are currently used for treatment of metastatic colorectal cancer. Although they have improved clinical outcome for these metastatic patients, only a small percentage benefit from the treatment. This limited efficacy is related to the lack of validated biomarkers that could aid better selection of the patients most likely to benefit. Although several biomarkers have been identified in recent years, we still do not know how to administer these drugs in a “personalized, targeted manner”. The purpose of this review is to summari...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Prognostic Impact of Deficient DNA Mismatch Repair and KRAS and BRAF
V600E Mutations in Patients with Lymph-Node-Positive Colon Cancer
Abstract
Although tumor stage remains the key determinant of colorectal cancer prognosis and treatment, there is considerable stage-independent variability in clinical outcome. Molecular markers hold promise for explaining variations in clinical behavior, and may identify patient subsets with differential efficacy and survival after adjuvant chemotherapy, which is the standard of care for patients with lymph-node-positive, i.e., stage III, colon cancer. An increased understanding of the molecular evolution and progression of colorectal cancer has identified two major pathways of tumorigenesis that are c...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Pulmonary Metastasectomy for Colorectal Cancer: Recent Reports Prompt a Review of the Available Evidence
Abstract
Pulmonary metastasectomy for colorectal cancer is commonplace surgery, but the practice has grown on the basis of follow-up studies. These studies base their conclusion on the effectiveness of metastasectomy on the survival rates at 5 years of very highly selected patients. Three publications in the last year, a registry study, a meta-analysis and a randomised controlled trial of monitoring and early detection of cancer recurrence, prompted a review of the evidence. A critical examination of the evidence suggests that much of the apparent benefit may be due to selection of patients most likely ...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Adjuvant Therapy in Combination with Resection of Colorectal Cancer Metastasis to the Liver or Lungs
Abstract
Surgical resection is associated with prolonged survival for patients with limited lung or liver metastatic colorectal cancer. The benefit of resection of colorectal liver metastases is widely accepted. However, after complete resection of colorectal liver metastases, up to 70 % of patients develop recurrence. Oncosurgical strategies, including complete resection and chemotherapy, have been developed to improve oncological outcome and to reduce recurrence after resection of colorectal liver metastases. Chemotherapy in combination with liver resection can be administered before, after, or befor...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Update on the Colon Health and Life-Long Exercise Change Trial: A Phase III Study of the Impact of an Exercise Program on Disease-Free Survival in Colon Cancer Survivors
Abstract
The Colon Health and Life-Long Exercise Change (CHALLENGE) trial is evaluating the effects of a 3-year exercise program on disease-free survival in 962 patients with resected high-risk stage II or stage III colon cancer. The purpose of this commentary is to provide an update on the CHALLENGE trial. As of December 31, 2013, the trial had randomized 250 patients in 20 Canadian centers and 26 Australian centers, with further expansion planned. Early barriers to accrual are reported and strategies to improve accrual are discussed. Of the 250 patients randomized to date, 89 % have stage III colon c...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
Adjuvant HIPEC in Colorectal Cancer
Abstract
Peritoneal carcinomatosis (PC) of colorectal origin has historically been regarded as fatal, with worse prognosis than other metastatic manifestations of the same origin. During the last three decades, complete cytoreductive surgery associated with adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) has led to improvement of outcome, with long-term survival being achieved for selected patients. This treatment is on the verge of becoming the standard of care for this metastatic disease. In this paper we review the rationale for HIPEC, the results obtained, and define its current indicatio...
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
To HIPEC or Not to HIPEC? That Is The Question
(Source: Current Colorectal Cancer Reports)
Source: Current Colorectal Cancer Reports - September 1, 2014 Category: Cancer & Oncology Source Type: research
