Abstract:
:Thymidylate synthase (TS) is a key enzyme in the synthesis of 2'-deoxythymidine-5'-monophosphate, an essential precursor for DNA biosynthesis. For this reason, this enzyme is a critical target in cancer chemotherapy. As the first TS inhibitor in clinical use, 5-fluorouracil (5-FU) remains widely used for the treatment of colorectal, pancreatic, breast, head and neck, gastric, and ovarian cancers. The reduced folate, leucovorin, has been shown to enhance the activity of 5-FU in colorectal cancer. However, response rates of the combination remain in the 25%-30% range, and much effort has been focused on designing new, more potent TS inhibitors. Raltitrexed is a folate analogue that is approved as first-line therapy for advanced colorectal cancer in Europe, Australia, Canada, and Japan, although it remains an investigational agent in the United States. Pemetrexed is an antifolate analogue that has shown promising activity in several solid tumor types, including mesothelioma. ZD9331, a highly specific TS inhibitor that dose not require polyglutamation for its activation, has shown activity in patients with refractory ovarian and colorectal cancer. Capecitabine is an oral fluoropyrimidine carbamate that was designed to generate 5-FU preferentially in tumor cells; this agent was recently approved by the US Food and Drug Administration as first-line therapy for patients with advanced colorectal cancer. As the number of TS inhibitors available for general clinical use increases, further research is needed to elucidate the critical molecular and biochemical elements that determine the efficacy and tumor specificity of each compound.
journal_name
Clin Colorectal Cancerjournal_title
Clinical colorectal cancerauthors
Rose MG,Farrell MP,Schmitz JCdoi
10.3816/CCC.2002.n.003keywords:
subject
Has Abstractpub_date
2002-02-01 00:00:00pages
220-9issue
4eissn
1533-0028issn
1938-0674pii
S1533-0028(11)70490-Xjournal_volume
1pub_type
杂志文章,评审abstract:INTRODUCTION:Bevacizumab improves outcome for patients with advanced colorectal cancer (CRC) when added to chemotherapy. The HORIZON I trial resulted in similar outcome with bevacizumab or cediranib, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor, as treatment of advanc...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clcc.2013.11.002
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:New treatment modalities and a growing understanding of the complex genetic tumor landscape have improved the outcome of colorectal cancer (CRC) patients. Nonetheless, more individualized treatment regimens, taking individual tumor characteristics into account, have been recently postulated and prognostic bi...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.02.008
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abstract:BACKGROUND:Anterior resection syndrome (ARS) is common after sphincter-saving surgery for rectal cancer. It includes changes in the frequency and urgency of bowel movements and fecal incontinence. The therapeutic efficacy of biofeedback on ARS is unclear. We sought to evaluate the effectiveness of biofeedback therapy i...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2015.11.002
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abstract::The multiplicity of chemotherapy regimens currently available to treat colorectal cancer in the first-line setting precludes the identification of a single standard regimen for front-line therapy. The previous standard, 5-fluorouracil (5-FU), formerly the only agent with any significant activity against colorectal can...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2004.s.002
更新日期:2004-06-01 00:00:00
abstract:PURPOSE:Our purpose is to perform a comprehensive literature review of the use of levoleucovorin in gastrointestinal malignancies and to assess whether levoleucovorin is a reasonable alternative to racemic leucovorin. DESIGN:This is an extensive literature review of levoleucovorin use in patients with gastrointestinal...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2009.n.034
更新日期:2009-10-01 00:00:00
abstract:INTRODUCTION:The aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS:In this double-blinded, phase II trial, patients with mCRC who had not progressed after 6...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clcc.2018.02.004
更新日期:2018-06-01 00:00:00
abstract::The use of adjuvant chemotherapy has improved survival in early-stage colon cancer. Ongoing adjuvant clinical trials are evaluating the addition of targeted therapies to standard chemotherapy regimen. Preliminary results with bevacizumab were disappointing. Also, cetuximab added to chemotherapy does not seem to be bet...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2010.n.039
更新日期:2010-12-01 00:00:00
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journal_title:Clinical colorectal cancer
pub_type: 临床试验,杂志文章
doi:10.3816/ccc.2004.n.026
更新日期:2004-11-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) has been validated as an important target in the treatment of metastatic colorectal cancer (mCRC). While initial studies focused on the treatment of disease that was refractory to available chemotherapy agents, 2 recent themes have emerged: the use of KRAS mutation status to sel...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2010.s.006
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND:Systemic chemotherapy increases the possibility of resection in patients with initially unresectable colorectal cancer (CRC), especially patients with hepatic metastasis. However, the predictive factors and prognosis of conversion to resection after chemotherapy in patients with various organ metastases rema...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2017.10.002
更新日期:2018-03-01 00:00:00
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journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2006.n.012
更新日期:2006-03-01 00:00:00
abstract::Combination protocols of 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan or oxaliplatin have demonstrated high activity in metastatic colorectal cancer. Capecitabine, an oral 5-FU prodrug, may replace infusional 5-FU/LV in combination protocols with irinotecan or oxaliplatin. We therefore initiated a phase II stud...
journal_title:Clinical colorectal cancer
pub_type: 临床试验,杂志文章
doi:10.3816/ccc.2004.n.009
更新日期:2004-05-01 00:00:00
abstract::Modern chemotherapy combinations for metastatic colorectal cancer (mCRC) comprise infusional 5-fluorouracil (5-FU), leucovorin, and irinotecan or oxaliplatin. The fluoropyrimidine derivative capecitabine is at least as effective as 5-FU plus leucovorin bolus regimens. It displays a favorable toxicity profile and offer...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2008.n.015
更新日期:2008-03-01 00:00:00
abstract::The discovery of the key role of the epidermal growth factor receptor (EGFR) and its downstream signaling effectors in the pathophysiology of colorectal cancer (CRC) has ushered in the clinical use of targeted therapies in the treatment of metastatic CRC (mCRC). The anti-EGFR monoclonal antibodies cetuximab and panitu...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2015.05.006
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:The safety of bevacizumab in older mCRC patients is poorly understood. The purpose of this analysis was to determine the prevalence, incidence, and risk factors for treatment-related AEs in older bevacizumab recipients. PATIENTS AND METHODS:Patients age ≥65 were identified from SEER-Medicare and categorized...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2012.11.004
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:As of 2006, bevacizumab was available for the treatment of metastatic colorectal cancer (mCRC) in British Columbia (BC). This study compares survival between referred patients diagnosed with mCRC in 2003/2004 (pre-bevacizumab era) and 2006 (bevacizumab era). PATIENTS AND METHODS:The BC cancer agency (BCCA) ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2011.03.004
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Individually, oxaliplatin and irinotecan have substantial activity in metastatic colorectal cancer (CRC) in combination with 5-fluorouracil/leucovorin. A combination regimen using all 4 agents could potentially increase response rates in CRC. PATIENTS AND METHODS:A multicenter phase II trial of oxaliplatin ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究
doi:10.3816/CCC.2007.n.017
更新日期:2007-05-01 00:00:00
abstract:BACKGROUND:Anal squamous cell carcinoma (ASCC) is a rare, human papilloma virus-associated cancer. The purpose was to investigate the population-based incidence rates, age and gender distribution, and survival of ASCC. MATERIALS AND METHODS:All primary ASCC in 1987 to 2016 were identified in the Cancer Registry of Nor...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.10.001
更新日期:2019-03-01 00:00:00
abstract::Microbiome (microbiota) is a community of all microorganisms inhabiting a specific site of the body, including pathogens, which distinguishes it from the physiological microflora. Intestinal dysbiosis plays a key role in the development of colorectal cancer. In the process of carcinogenesis, inflammation, immune respo...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2019.07.006
更新日期:2020-03-01 00:00:00
abstract::Bevacizumab is a humanized monoclonal antibody approved by the US Food and Drug Administration for use in combination with fluorouracil (FU)-based chemotherapy for first-line treatment of patients with metastatic colorectal carcinoma (CRC). Its mechanism of action is inhibition of tumor angiogenesis by neutralizing va...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2010.n.008
更新日期:2010-01-01 00:00:00
abstract::Primary squamous cell colorectal carcinomas are uncommon, and their characteristics are not well known. They seem to occur most commonly in the fifth decade of life with a slight predominance for men. The most commonly reported anatomic locations are the rectum and the proximal colon. Clinical features and common diag...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2001.n.006
更新日期:2001-05-01 00:00:00
abstract::Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal cancer of teh gastrointestinal tract. They are characterized by the expression of KIT. Therapeutically, metastatic GISTs are effectively treated by imatinib, a tyrosine kinase inhibitor (TKI) with activity against KIT and platelet-derived growth f...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2006.s.005
更新日期:2006-11-01 00:00:00
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journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2014.02.001
更新日期:2014-09-01 00:00:00
abstract:INTRODUCTION:Hepatic arterial infusion chemotherapy (HAIC) is a treatment used for liver metastases (LM) of colorectal cancer (CRC). Because of its technical conditions, it has been used in only a few experienced centers in France. Our aim was to evaluate its feasibility, efficacy and tolerance in 4 centers. METHODS:C...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clcc.2017.03.003
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:The prognostic value of tumor sidedness in metastatic colorectal cancer (CRC) has been established, but its impact on nonmetastatic disease remains unclear. Our study aimed to explore the prognostic effect of tumor sidedness by subgroup survival analyses, according to histology and tumor grade in stage I-IV ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.10.005
更新日期:2019-03-01 00:00:00
abstract::Several anticancer therapies have been developed to block angiogenesis, a key mechanism in tumor growth and metastasis. The predominantly cytostatic action of these compounds makes an assessment of their clinical activities inadequate if based only on the reduction of the tumor dimensions, as this may not reflect thei...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2014.12.002
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Screening protocols for colorectal cancer are broadly recommended and effective in reducing mortality. However, populations from different age groups can harbor distinct pathologic and molecular profiles that can also be influenced by screening and polyp resection, especially in older ages. PATIENTS AND MET...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2020.06.004
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Their real-life evaluation is insufficient, especially in elderly and frail patients. The aim was to describe use, safety, and effectiveness of targeted therapies in first-line mCRC treatment according to age. PATIENTS AND...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.11.005
更新日期:2019-03-01 00:00:00
abstract::The development of brain metastases originating from colorectal cancer (CRC) is an infrequent phenomenon occurring in < 5% of patients. Yet, it is feasible that physicians will be diagnosing more patients with brain metastases because of the prolonged survival in our current patient population. The anti-angiogenic age...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2008.n.010
更新日期:2008-01-01 00:00:00
abstract::Adjuvant therapy can reduce the risk of disease recurrence in patients with stage II-IV colorectal cancer. Recently, 3 monoclonal antibodies have been shown to improve clinical outcome in this group of patients. Bevacizumab is an antiangiogenesis agent that has been shown in clinical and preclinical models to reverse ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2007.n.004
更新日期:2007-01-01 00:00:00