Polo-Like Kinases in Colorectal Cancer: Potential for Targeted Therapy
Abstract
The five individual members of the mammalian polo-like kinase family play non-redundant roles in centriole replication and maturation, mitotic progression, cytokinesis, and the DNA damage response. In human colorectal cancer, Plk1 and Plk4 are expressed at higher levels in tumor than adjacent normal mucosa, and the degree of overexpression correlates with adverse prognosis. In colorectal cancer cell lines, suppression of Plk1 activity leads to mitotic arrest and apoptosis, while inhibition of Plk4 activity reduces tumor growth and invasion. Inhibition of Plk1 or Plk4 in mice using orally bioavail...
Source: Current Colorectal Cancer Reports - June 6, 2015 Category: Cancer & Oncology Source Type: research
Management of the Primary Colorectal Cancer and Synchronous Liver Metastases
Abstract
In the last two decades, advances in liver surgery and systemic therapy have increased the scope and complexity of curative treatment of metastatic colorectal cancer. Synchronous liver metastasis represents a particularly challenging scenario where resection of the primary cancer and liver disease should be contemplated while still offering systemic therapy. Different treatment sequences have been proposed aiming to optimize long-term survival and decrease cumulative treatment-related morbidity. Safety and feasibility of colorectal-first, combined, and liver-first approaches have been demonstrate...
Source: Current Colorectal Cancer Reports - June 3, 2015 Category: Cancer & Oncology Source Type: research
Current Status of Imaging to Evaluate Liver Metastases From Colorectal Cancer
Abstract
Multiple imaging modalities are routinely used to identify, characterize, and clinically follow colorectal cancer liver metastases. These include ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography. Within each modality, there exist multiple variations of protocol, which could include addition of contrast, acquisition of specific imaging sequences, or combination of images with those of another modality. In addition to considerations of imaging protocols and equipment, one must also consider patient-specific factors to determine appropriate imaging for co...
Source: Current Colorectal Cancer Reports - May 28, 2015 Category: Cancer & Oncology Source Type: research
Conversion Chemotherapy for Unresectable Colorectal Liver Metastases: Are We Making a Difference?
Abstract
Surgical resection remains the only curative therapy for colorectal liver metastases (CLM) with 5-year survival rates ranging from 40 to 58 %. Unfortunately, only approximately 15–25 % of patients are eligible for initial surgical resection. Among those that are unresectable, response to chemotherapy can convert an additional 15–20 % of unresectable patients to a potentially resectable state and offer curative-intent resection. In this select group of patients undergoing resection following conversion chemotherapy, 5-year survival rates approach 50 %. Despite a slightly shorter time to re...
Source: Current Colorectal Cancer Reports - May 6, 2015 Category: Cancer & Oncology Source Type: research
How to Identify the Right Patients for the Right Treatment in Metastatic Colorectal Cancer (mCRC)
Abstract
A major challenge in metastatic colorectal cancer (mCRC) is the identification of specific biomarkers that are likely to predict which patients will benefit from a specific treatment, especially in recent years, that available options have substantially increased with the introduction of novel targeted therapies. To this date, a number of studies have shown that a tumor mutational profile influences outcome in mCRC patients treated with an anti-epidermal growth factor receptor (anti-EGFR)-targeting agent and should, therefore, be used to guide treatment decision. Despite our undeniable progress t...
Source: Current Colorectal Cancer Reports - April 30, 2015 Category: Cancer & Oncology Source Type: research
Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New Perspectives
Abstract
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 anti-tumor immune cells against malignancies nor conclusively or consistently granted protection, complete remissi...
Source: Current Colorectal Cancer Reports - April 29, 2015 Category: Cancer & Oncology Source Type: research
n-3 PUFAs: an Elixir in Prevention of Colorectal Cancer
Abstract
Dietary fats especially essential unsaturated fatty acids have been proven to be major determinants in cancer progression and propagation. Epidemiological and experimental data indicates that consumption of higher amounts of n-6 PUFAs with respect to n-3 PUFAs increases the predisposition to various diseases including colon cancer. The chemopreventive effect of n-3 PUFAs has been ascribed to the replacement of n-6 PUFAs in cell membrane-associated lipid rafts. The change in architecture of their lipid rafts influences the behavior of membrane-bound proteins and receptors, and thereby, modulation ...
Source: Current Colorectal Cancer Reports - April 20, 2015 Category: Cancer & Oncology Source Type: research
Reviewing the Role of Aspirin in Chemoprevention of Colorectal Cancer
Abstract
A substantial number of observational and interventional studies support the role of aspirin as preventive agent in many types of cancer, especially in colorectal cancer (CRC). Low-dose aspirin (75–325 mg), used for at least 5 years, appear to reduce the incidence of adenomas and CRC mortality. Those benefits apply not only for the general population but also for people with pre-existing adenomas and CRC history. Both the inhibition of cyclooxygenase (COX)-1 and COX-2 are implicated in the mechanism of action of aspirin and are important in the role of chemoprevention in CRC. However, in the ...
Source: Current Colorectal Cancer Reports - April 18, 2015 Category: Cancer & Oncology Source Type: research
The Molecular Taxonomy of Colorectal Cancer: What’s New?
Abstract
Colorectal cancer is a highly complex and heterogeneous disease. Since Vogelstein’s description of a colorectal cancer model almost 30 years ago, significant advances have been made to better characterize and classify colorectal tumors. The technological advances in the past few years have favored a deeper analysis of the genetic and epigenetic features that characterize colorectal tumors, leading to several molecular classifications. Although not always consistent, these analyses have shed light on the molecular features that shape colorectal tumors. In recent times, consensus groups and coll...
Source: Current Colorectal Cancer Reports - April 13, 2015 Category: Cancer & Oncology Source Type: research
Hereditary Non-polyposis Colorectal Cancer: Prevention and Therapeutic Options
Abstract
Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common hereditary colorectal cancer (CRC) syndrome. The first and foremost preventive measure is to identify patients with LS among CRC patients. This requires the screening of colorectal cancer through polymerase chain reaction-based microsatellite instability (MSI) testing or immunohistochemistry to look for a loss of expression of one of the mismatch repair (MMR) proteins and the referral of selected patients to genetic counseling. In LS patients, annual or biannual complete colonoscopy with chro...
Source: Current Colorectal Cancer Reports - March 19, 2015 Category: Cancer & Oncology Source Type: research
Colorectal Surgery in Lynch Syndrome Patients: When and How?
Abstract
Lynch syndrome is the most common inherited colorectal cancer susceptibility syndrome and accounts for approximately 3 % of all colorectal cancers. Clinical assessment and a detailed family history are crucial in identifying patients who need further evaluation via genetic counseling and testing. Discovery of the underlying causative germline mutations in DNA mismatch repair genes has allowed more accurate colorectal and extracolonic cancer risk assignment. Once diagnosed, intensive surveillance via colonoscopy and timely interventions such as polypectomy reduce colorectal cancer development and...
Source: Current Colorectal Cancer Reports - March 17, 2015 Category: Cancer & Oncology Source Type: research
Immunotherapeutic Strategies for Colon Cancer: Monoclonal Antibody Therapy
Abstract
Colorectal cancer continues to be a leading cause of cancer mortality and morbidity in developed nations and is on the rise in developing countries. In metastatic setting, systemic therapy provides palliation and overall survival advantage as proved in multiple clinical trials. Unfortunately, the survival benefit often comes at the cost of significant toxicities in the recipients. The emerging data of immunotherapy and recent advancements in understanding of immune cells, cytokines, and their roles in cancer pathogenesis have shed some light in our search for the new approaches of combating cance...
Source: Current Colorectal Cancer Reports - March 10, 2015 Category: Cancer & Oncology Source Type: research
Role of Cytoreduction Surgery With HIPEC in the Management of Peritoneal Carcinomatosis From Colorectal Cancer and Pseudomyxoma Peritonei
Abstract
For most cancers, peritoneal carcinomatosis (PC) usually is considered a systemic disease and portends a very poor prognosis. However, in colorectal cancer, especially the mucinous colorectal adenocarcinoma (MCA) subtype and epithelial appendiceal neoplasms—particularly pseudomyxoma peritonei (PMP)—the pattern of PC represents local celomic extension of disease rather than systemic metastasis. Among the treatment options for isolated PC, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the de facto standard of care in many institutions, based on pr...
Source: Current Colorectal Cancer Reports - February 21, 2015 Category: Cancer & Oncology Source Type: research
First-Line Therapy in Metastatic Colorectal Cancer Patients Not Candidates for Curative Surgery
Abstract
Metastatic colorectal cancer (CRC) is a significant cause of morbidity and mortality around the world. Novel cytotoxic and biologic therapies have been developed; however, their optimal use in terms of patient selection, drug combinations, and regimen sequences must be better defined. The FDA-approved drugs include fluoropyrimidines (5-fluorouracil (5-FU) with or without leucovorin (LV), capecitabine), irinotecan, oxaliplatin, the vascular endothelial growth factor (VEGF) antibody bevacizumab, the epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab for RAS wild-type patie...
Source: Current Colorectal Cancer Reports - February 18, 2015 Category: Cancer & Oncology Source Type: research
Is There a Role for Adjuvant Chemotherapy in Rectal Cancer?
Abstract
Adjuvant chemoradiotherapy trials demonstrated a reduction in local failure and an increase in survival of patients with locally advanced rectal cancer submitted to upfront surgery. The standard-of-care shifted to neoadjuvant chemoradiotherapy when the German Rectal Cancer Study Group Trial demonstrated the benefit of neoadjuvant compared to adjuvant fluoropyrimidine chemoradiotherapy in lower rates of local failure, lower toxicity in patients optimally resected with total mesorectal excision (TME), and higher rate of sphincter-sparing surgery. Overall survival (OS) was equivalent in both arms. T...
Source: Current Colorectal Cancer Reports - February 15, 2015 Category: Cancer & Oncology Source Type: research
