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goal directed therapy in colorectal cancer

Shyam S Mohapatra, Surinder K Batra, Srinivas Bharadwaj, Michael Bouvet, Bard Cosman, Ajay Goel, Wilma Jogunoori, Michael J Kelley, Lopa Mishra, Bibhuti Mishra, Subhra Mohapatra, Bhaumik Patel, Joseph R Pisegna, Jean-Pierre Raufman, Shuyun Rao, Hemant Roy, Maren Scheuner, Satish Singh, Gitanjali Vidyarthi, Jon White
Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches...
March 23, 2018: Digestive Diseases and Sciences
Luai R Zarour, Sudarshan Anand, Kevin G Billingsley, William H Bisson, Andrea Cercek, Michael F Clarke, Lisa M Coussens, Charles E Gast, Cristina B Geltzeiler, Lissi Hansen, Katherine A Kelley, Charles D Lopez, Shushan R Rana, Rebecca Ruhl, V Liana Tsikitis, Gina M Vaccaro, Melissa H Wong, Skye C Mayo
In patients with colorectal cancer (CRC) that metastasizes to the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. Although new therapeutic regimens developed over the past decade have increased survival, there is substantial room for improvement in selecting targeted treatment regimens for the patients who will derive the most benefit. Recently, there have been exciting developments in identifying high-risk patient cohorts, refinements in the understanding of systemic vs localized drug delivery to metastatic niches, liquid biomarker development, and dramatic advances in tumor immune therapy, all of which promise new and innovative approaches to tackling the problem of detecting and treating the metastatic spread of CRC to the liver...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
M G Zampino, E Magni, P S Ravenda, C A Cella, G Bonomo, P Della Vigna, S Galdy, F Spada, G M Varano, G Mauri, N Fazio, F Orsi
A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival...
December 2016: Critical Reviews in Oncology/hematology
Salvatore Siena, Josep Tabernero, Gyorgy Bodoky, David Cunningham, Fernando Rivera, Paul Ruff, Jean Luc Canon, Reija Koukakis, Gaston Demonty, Guy Hechmati, Jean-Yves Douillard
INTRODUCTION: Metastatic colorectal cancer is rarely curable. Improving quality of life is therefore a key treatment goal. We report quality of life for patients with RAS wild-type metastatic colorectal cancer in the PRIME study. METHODS: A randomised phase 3 open-label study of first-line panitumumab+FOLFOX4 vs FOLFOX4 enrolled adults with untreated metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status of 0-2. This analysis includes patients with wild-type RAS tumours (n=505)...
2016: ESMO Open
Mark H O'Hara, Stanley R Hamilton, Peter J O'Dwyer
Advances in the understanding of genomic alterations in cancer, and the various therapies targeted to these alterations have permitted the design of trials directed to bringing this science to the clinic, with the ultimate goal of tailoring therapy to the individual. There is a high need for advances in targeted therapy in colorectal cancer, a disease in which only 2 classes of targeted therapies are approved for use in colorectal cancer, despite the majority of colorectal cancers containing a potentially targetable mutation...
May 2016: Cancer Journal
Hwan-Seok Jeong, Hyosook Hwang, Phil-Sun Oh, Eun-Mi Kim, Tai Kyoung Lee, Minjoo Kim, Hyeon Soo Kim, Seok Tae Lim, Myung-Hee Sohn, Hwan-Jeong Jeong
The goal of the study described here was to evaluate the use of high-intensity focused ultrasound (HIFU) in drug release and its application in cancer therapy. HIFU was set to minimize hyperthermia, particularly non-specific hyperthermia, of exposed areas. An in vitro temperature-sensitive hydrogel phantom model determined the parameters of HIFU under mild condition settings (spatial average temporal average intensity [ISATA] = 83.35 W/cm(2)). PEGylated liposomal indocyanine green (LCLP-ICG) and PEGylated liposomal doxorubicin (LCLP-Dox) were prepared with the same mole ratio to allow direct comparison of drug release in vitro and in vivo...
April 2016: Ultrasound in Medicine & Biology
Nasser Alsanea, Majid A Almadi, Alaa S Abduljabbar, Samar Alhomoud, Taghreed A Alshaban, Abdullah Alsuhaibani, Ahmad Alzahrani, Faisal Batwa, Abdul-Hameed Hassan, Denise Hibbert, Randa Nooh, Mohammed Alothman, Bram Rochwerg, Waleed Alhazzani, Rebecca L Morgan
BACKGROUND: Colorectal cancer is the most common cancer among Saudi men and the third commonest among Saudi women. Given the predominance of colorectal cancer compared with other cancers in Saudi Arabia, context-specific guidelines are needed for screening. METHODS: Experts from the Saudi Society of Colon and Rectal Surgery, Saudi Gastroenterology Association, Saudi Oncology Society, Saudi Chapter of Enterostomal Therapy, Family Medicine and Department of Public Health at the Saudi Arabian Ministry of Health and a patient advocate was assembled by the Saudi Centre for Evidence-Based Healthcare, a subsidiary of the Saudi Arabian Ministry of Health...
May 2015: Annals of Saudi Medicine
Michael J Reiter, Nathan P Hannemann, Ryan B Schwope, Christopher J Lisanti, Peter A Learn
Surgical resection of colorectal metastatic disease has increased as surgeons have adopted a more aggressive ideology. Current exclusion criteria are patients for whom a negative resection margin is not feasible or a future liver remnant (FLR) of greater than 20% is not achievable. The goal of preoperative imaging is to identify the number and distribution of liver metastases, in addition to establishing their relation to relevant intrahepatic structures. FLR can be calculated utilizing cross-sectional imaging to select out patients at risk for hepatic dysfunction after resection...
October 2015: Abdominal Imaging
Margaret E Clark, Richard R Smith
Colorectal cancer (CRC) is a major health concern in the United States (US) with over 140,000 new cases diagnosed in 2012. The most common site for CRC metastases is the liver. Hepatic resection is the treatment of choice for colorectal liver metastases (CLM), with a 5-year survival rate ranging from 35% to 58%. Unfortunately, only about 20% of patients are eligible for resection. There are a number of options for extending resection to more advanced patients including systemic chemotherapy, portal vein embolization (PVE), two stage hepatectomy, ablation and hepatic artery infusion (HAI)...
October 2014: Journal of Gastrointestinal Oncology
Jessica Mitchell, Taline Khoukaz, Deborah McNeal, Lori Brent
Patients with metastatic colorectal cancer (mCRC) frequently experience treatment-related adverse events (AEs), which may lead to nonadherence or discontinuation from their treatment regimen. In the phase 3 CORRECT study, the addition of regorafenib to best supportive care (BSC) significantly increased overall survival and progression-free survival compared with placebo plus BSC in patients with mCRC who had progressed on all approved standard care therapies. Although regorafenib showed an acceptable safety profile, patients experienced treatment-related AEs such as hand-foot skin reaction, hypertension, oral mucositis, diarrhea, fatigue, and liver abnormalities...
April 2014: Clinical Journal of Oncology Nursing
Elizabeth McKeown, Daniel W Nelson, Eric K Johnson, Justin A Maykel, Alexander Stojadinovic, Aviram Nissan, Itzhak Avital, Björn Ldm Brücher, Scott R Steele
INTRODUCTION: With the advent of multidisciplinary and multimodality approaches to the management of colorectal cancer patients, there is an increasing need to define how we monitor response to novel therapies in these patients. Several factors ranging from the type of therapy used to the intrinsic biology of the tumor play a role in tumor response. All of these can aid in determining the ideal course of treatment, and may fluctuate over time, pending down-staging or progression of disease...
2014: Journal of Cancer
Skye C Mayo, Carlo Pulitano, Hugo Marques, Jorge Lamelas, Christopher L Wolfgang, Wassila de Saussure, Michael A Choti, Isabelle Gindrat, Luca Aldrighetti, Eduardo Barrosso, Gilles Mentha, Timothy M Pawlik
BACKGROUND: The goal of this study was to investigate the surgical management and outcomes of patients with primary colorectal cancer (CRC) and synchronous liver metastasis (sCRLM). STUDY DESIGN: Using a multi-institutional database, we identified 1,004 patients treated for sCRLM between 1982 and 2011. Clinicopathologic and outcomes data were evaluated with uni- and multivariable analyses. RESULTS: A simultaneous CRC and liver operation was performed in 329 (33%) patients; 675 (67%) underwent a staged approach ("classic" staged approach, n = 647; liver-first strategy, n = 28)...
April 2013: Journal of the American College of Surgeons
Magali Terme, Simon Pernot, Elie Marcheteau, Federico Sandoval, Nadine Benhamouda, Orianne Colussi, Olivier Dubreuil, Antoine F Carpentier, Eric Tartour, Julien Taieb
Multitarget antiangiogenic tyrosine kinase inhibitors (TKI) have been shown to reduce regulatory T cells (Treg) in tumor-bearing animals and patients with metastatic renal carcinomas. However, a direct role of the VEGF-A/VEGFR pathway inhibition in this phenomenon is a matter of debate and molecular mechanisms leading to Treg modulation in this setting have not been explored to date. Treg proportion, number, and proliferation were analyzed by flow cytometry in peripheral blood of patients with metastatic colorectal cancer (mCRC) treated with bevacizumab, a monoclonal antibody targeting specifically VEGF-A, and in colon cancer-bearing mice (CT26) treated with drugs targeting the VEGF/VEGFR axis...
January 15, 2013: Cancer Research
Aruna S Jaiswal, Sanjeev Banerjee, Ritu Aneja, Fazlul H Sarkar, David A Ostrov, Satya Narayan
Chemoprevention presents a major strategy for the medical management of colorectal cancer. Most drugs used for colorectal cancer therapy induce DNA-alkylation damage, which is primarily repaired by the base excision repair (BER) pathway. Thus, blockade of BER pathway is an attractive option to inhibit the spread of colorectal cancer. Using an in silico approach, we performed a structure-based screen by docking small-molecules onto DNA polymerase β (Pol-β) and identified a potent anti-Pol-β compound, NSC-124854...
February 2, 2011: PloS One
Peter M Wilson, Heinz-Josef Lenz
The advent of pharmacogenetics and its underlying concept that disparities in drug metabolism, efficacy, and toxicity are determined by the genetic makeup of an individual has birthed the concept and promise of 'tailored medicine.' One such facet of medicine that serves to benefit greatly from this tailored approach is the implementation of chemotherapy in cancer treatment. The past decade has witnessed significant advances in the treatment of colorectal cancer (CRC); however, tumor drug resistance remains a major obstacle in CRC treatment, and many patients do not receive any clinical benefit from chemotherapy...
June 2010: Clinical Colorectal Cancer
Ryan Whitney, Cliff Tatum, Mike Hahl, Susan Ellis, Charles R Scoggins, Kelly McMasters, Robert C G Martin
BACKGROUND: Unresectable hepatic metastases from aerodigestive cancers are common and in most cases herald a poor prognosis. A small percentage of patients maybe amenable to surgical resection or ablation once the biology of the disease and the burden of hepatic disease are better understood. The use of hepatic arterial resin microspheres containing the β emitter, yttrium-90, has been reported in the treatment of unresectable hepatic metastases. The goal of this review was to evaluate the use of yttrium-90 hepatic arterial therapy in the management of hepatic metastases and surgical downstaging...
April 2011: Journal of Surgical Research
Robert D Timmerman, Costas S Bizekis, Harvey I Pass, Yuman Fong, Damian E Dupuy, Laura A Dawson, David Lu
Because local therapies directed toward a specific tumor mass are known to be effective for treating early-stage cancers, it should be no surprise that there has been considerable historical experience using local therapies for metastatic disease. In more recent years, increasing interest in the use of local therapy for metastases likely has arisen from improvements in systemic therapy. In the absence of effective systemic therapies, such local treatments were often considered futile given both the difficulty in eliminating all sites of identifiable metastatic disease as well as realities regarding the rapid natural history of uncontrolled tumor dissemination...
May 2009: CA: a Cancer Journal for Clinicians
Ki-Tae Suk, Hyun-Soo Kim
Individualized tailored therapy is a currently pursuing direction for improving the outcome of patients with colorectal cancer. Targeted therapy is the potential strategy to reach this goal by evaluating status of the presumed targets and their related effector molecules and by maximizing the efficacy of chemotherapeutic agents with less toxicity in individual patient. Numerous hurdles should be overcome, however, because therapeutic outcome can be affected by multiple components; tumor characteristics such as somatic mutations at the DNA, RNA, and protein levels; patient characteristics like germline genetic polymorphisms in enzymes linked to drug metabolism; and environmental factors that include diet and physical activity...
February 2009: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
Ashish Garg, Alison W Tisdale, Eman Haidari, Efrosini Kokkoli
Integrin alpha(5)beta(1) is expressed on several types of cancer cells, including colon cancer, and plays an important role in tumor growth and metastasis. The ability to target the integrin alpha(5)beta(1) using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth, reducing tumor metastasis, and decreasing deleterious side effects associated with different cancer therapies. Liposomes are nano-sized phospholipid bilayer vesicles that have been extensively studied as drug delivery carriers...
January 21, 2009: International Journal of Pharmaceutics
W Buffet, K P Geboes, G Dehertogh, K Geboes
BACKGROUND: Epidermal Growth Factor Receptor (EGFR)-targeted therapies are currently used for the treatment of metastasized colorectal cancer (CRC) and non small cell lung cancer (NSCLC). Patient selection for this treatment is based on immunohistochemical (IHC) testing for EGFR. The rising amount of commercially available EGFR-antibodies makes standardisation of EGFR-IHC necessary. The goal of this study was to analyse possible discrepancies between 3 antibodies against EGFR. PATIENTS AND METHODS: 36 formalin-fixed samples of CRC (n = 26) and NSCLC (n = 10) were stained with 3 antibody-clones: 2-18C9 (Dako); 31G7 (VentanaTM) and 111...
April 2008: Acta Gastro-enterologica Belgica
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