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Metastatic colorectal cancer

Sara Crotti, Martina Piccoli, Flavio Rizzolio, Antonio Giordano, Donato Nitti, Marco Agostini
Colorectal cancer (CRC) whit more than a million of new cases per year is one of the most common registered cancers worldwide with few treatment options especially for advanced and metastatic patients. The tumor microenvironment is composed by extracellular matrix (ECM), cells and interstitial fluids. Among all these constituents, in the last years an increased interest around the ECM and its potential role in cancer tumorigenesis is arisen. During cancer progression the ECM structure and composition became disorganized, allowing cellular transformation and metastasis...
October 24, 2016: Journal of Cellular Physiology
Gabriele Picco, Consalvo Petti, Francesco Sassi, Katia Grillone, Giorgia Migliardi, Teresa Rossi, Claudio Isella, Federica Di Nicolantonio, Ivana Sarotto, Anna Sapino, Alberto Bardelli, Livio Trusolino, Andrea Bertotti, Enzo Medico
BACKGROUND: The NEDD8 conjugation pathway modulates the ubiquitination and activity of a wide range of intracellular proteins, and its blockade by pevonedistat is emerging as a promising therapeutic approach in various cancer settings. However, systematic characterization of pevonedistat efficacy in specific tumor types and definition of response predictors are still missing. METHODS: We investigated in vitro sensitivity to pevonedistat in 122 colorectal cancer (CRC) cell lines by an ATP-based proliferation assay and evaluated apoptosis and DNA content by flow cytometry...
February 2017: Journal of the National Cancer Institute
(no author information available yet)
Findings from a phase I/II study indicate a higher response rate among patients with BRAF-mutant metastatic colorectal cancer treated with an EGFR inhibitor alongside dual, as opposed to single-level, MAPK blockade. Panitumumab combined with trametinib and dabrafenib only modestly increased median progression-free survival, however; a short-lived decrease in responders' BRAF V600E mutant allele fraction and the emergence of RAS mutations may have been contributing factors.
October 21, 2016: Cancer Discovery
Yong-Xia Wang, Yan-Ru Chen, Shan-Shan Liu, Ya-Ping Ye, Hong-Li Jiao, Shu-Yang Wang, Zhi-Yuan Xiao, Wen-Ting Wei, Jun-Feng Qiu, Li Liang, Wen-Ting Liao, Yan-Qing Ding
Colorectal cancer (CRC) is the third most common cancer worldwide. Metastatic progression is a primary factor contributing to lethality of CRC patients. However, the molecular mechanisms forming early local invasion and distant metastatic colonies are still unclear and the present therapeutic approaches for CRC are unsatisfactory. Therefore, novel therapies targeting metastatic invasion that could prevent tumor spreading and recurrence are urgently needed. Our study showed that the decrease of miR-384 was found in 83...
October 17, 2016: Oncotarget
Raymond Chan, Patsy Yates, Alexandra L McCarthy
PURPOSE/OBJECTIVES: To explore the fatigue self-management behaviors and factors associated with effectiveness of these behaviors in patients with advanced cancer.
. DESIGN: Prospective longitudinal interviewer-administered survey.
. SETTING: Royal Brisbane and Women's Hospital in Queensland, Australia.
. SAMPLE: 152 outpatients with metastatic breast, lung, colorectal, and prostate cancer experiencing fatigue were recruited...
November 1, 2016: Oncology Nursing Forum
Laura Schirosi, Annalisa Mazzotta, Giuseppina Opinto, Rosamaria Pinto, Giusi Graziano, Stefania Tommasi, Livia Fucci, Giovanni Simone, Anita Mangia
There is an increasing need to identify new biomarkers in colorectal cancer (CRC) to further characterize this malignancy. β-catenin plays a central role in the Wnt signaling pathway. It also binds Na+/H+ exchanger regulating factor 1 (NHERF1) and interacts with the RAS-association domain family 1, isoform A (RASSF1A), but the mechanisms of this possible crosstalk are still not fully understood. In this study, we analyzed for the first time the different subcellular expression of β-catenin, NHERF1, and RASSF1A and their relationships with RASSF1A methylation in the progression of CRC...
September 27, 2016: Oncotarget
Meinolf Karthaus, Ralf-Dieter Hofheinz, Laurent Mineur, Henry Letocha, Richard Greil, Josef Thaler, Eva Fernebro, Kelly S Oliner, Michael Boedigheimer, Brian Twomey, Ying Zhang, Gaston Demonty, Claus-Henning Köhne
BACKGROUND: To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC). METHODS: 154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression. RESULTS: Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease...
October 20, 2016: British Journal of Cancer
Chao Fang, Chuanwen Fan, Cun Wang, Qiaorong Huang, Wentong Meng, Yongyang Yu, Lie Yang, Zhihai Peng, Jiankun Hu, Yuan Li, Xianming Mo, Zongguang Zhou
INTRODUCTION: Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM). RESULTS: The expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0...
October 15, 2016: Oncotarget
Satoshi Nagase, Tomokazu Iyoda, Hiroshi Kanno, Tomohide Akase, Ichiro Arakawa, Tadao Inoue, Yoshio Uetsuka
Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Dimitar K Penchev, Lilyana V Vladova, Miroslav Z Zashev, Radosvet P Gornev
AIM: To assess the effect of the factor 'hepatic metastatic disease' on long-term outcomes in patients with colorectal cancer. MATERIALS AND METHODS: We analysed retrospectively 200 randomly selected patients. Forty-two of them were excluded from the study for different reasons so the study contingent was 158 patients over a period of 23 years. All were diagnosed and treated in the Lozenetz University Hospital, in the Department of General Surgery. 125 of the patients were diagnosed with colorectal cancer without distant metastases and 33 of the patients had liver metastases as a result of colorectal carcinoma...
September 1, 2016: Folia Medica
Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
BACKGROUND: Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. METHODS: Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer Panel(TM), MiSeq sequencing and data analyses (Illumina)...
October 18, 2016: Molecular Cancer
J Quidde, S Hegewisch-Becker, U Graeven, C A Lerchenmüller, B Killing, R Depenbusch, C-C Steffens, T Lange, G Dietrich, J Stoehlmacher, A Reinacher, A Tannapfel, T Trarbach, N Marschner, H-J Schmoll, A Hinke, S-E Al-Batran, D Arnold
BACKGROUND: First-line maintenance strategies are a current matter of debate in the management of mCRC. Their impact on patient's health-related quality of life (HRQOL) has not yet been evaluated. The objective of this study was to assess whether differences in HRQOL during any active maintenance treatment compared with no maintenance treatment exist. PATIENT AND METHODS: Eight hundred and thirty-seven patients were enrolled in the AIO KRK 0207 trial. Four hundred and seventy-two underwent randomization (after 24 weeks of induction treatment) into one of the maintenance arms: FP plus Bev (arm A), Bev alone (arm B), or no active treatment (arm C)...
October 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Olivier Mir, Thomas Brodowicz, Antoine Italiano, Jennifer Wallet, Jean-Yves Blay, François Bertucci, Christine Chevreau, Sophie Piperno-Neumann, Emmanuelle Bompas, Sébastien Salas, Christophe Perrin, Corinne Delcambre, Bernadette Liegl-Atzwanger, Maud Toulmonde, Sarah Dumont, Isabelle Ray-Coquard, Stéphanie Clisant, Sophie Taieb, Cécile Guillemet, Maria Rios, Olivier Collard, Laurence Bozec, Didier Cupissol, Esma Saada-Bouzid, Christine Lemaignan, Wolfgang Eisterer, Nicolas Isambert, Loïc Chaigneau, Axel Le Cesne, Nicolas Penel
BACKGROUND: Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline. METHODS: In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment...
October 14, 2016: Lancet Oncology
Santiago Marfà, Josep Marti, Adalgiza Reyes, Gregori Casals, Guillermo Fernández-Varo, Silvia Carvajal, J C García-Valdecasas, Josep Fuster, Wladimiro Jiménez
Colorectal cancer (CRC) is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs). During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as "mild" or "severe" based on the 5-year survival...
October 2016: Translational Oncology
Mark A Healy, Jason C Pradarelli, Robert W Krell, Scott E Regenbogen, Pasithorn A Suwanabol
BACKGROUND: Despite substantially improved survival with metastatic site resection in colorectal cancers, uptake of aggressive surgical approaches remains low among certain patients. It is unknown whether financial determinants of care, such as insurance status, play a role in this treatment gap. OBJECTIVE: We sought to evaluate the effect of insurance status on metastasectomy in patients with advanced colorectal cancers. DESIGN: This was a retrospective cohort study...
November 2016: Diseases of the Colon and Rectum
Hailong Zhang, Liang Qiao, Xiaopeng Li, Yang Wan, Li Yang, Huijuan Wang
Lymph node metastasis is a decisive prognostic and therapeutic staging factor for colorectal cancer (CRC), which is one of the most prevalent types of cancer and a malignant tumor. The metabolic profiling of tissue samples from a large cohort of lymph node non‑metastatic CRC patients (n=73), lymph node metastatic CRC patients (n=52) and normal controls (n=41) was performed using 1H nuclear magnetic resonance (NMR) together with multivariate statistical analyses. Excellent separation was obtained between CRC patients and normal controls, and CRC patients were also perfectly classified according to lymph node metastasis...
October 14, 2016: Oncology Reports
Zhao-Wei Zou, Hai-Jin Chen, Jin-Long Yu, Zong-Hai Huang, Shun Fang, Xiao-Hua Lin
Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5‑fluorouracil (5‑FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock‑down...
October 6, 2016: Molecular Medicine Reports
Carmine Pinto, Francesca Di Fabio, Gerardo Rosati, Ivan R Lolli, Enzo M Ruggeri, Libero Ciuffreda, Daris Ferrari, Giovanni Lo Re, Giovanni Rosti, Paolo Tralongo, Raimondo Ferrara, Oscar Alabiso, Silvana Chiara, Giovanni P Ianniello, Antonio Frassoldati, Domenico Bilancia, Giovanna A Campanella, Carlo Signorelli, Patrizia Racca, Elena Benincasa, Maria Elena Stroppolo, Francesco Di Costanzo
Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30...
October 17, 2016: Cancer Medicine
Rohan C Parikh, Xianglin L Du, Robert O Morgan, David R Lairson
BACKGROUND: Over the last decade, multiple chemotherapies/targeted biologics have been approved for metastatic colorectal cancer (mCRC). However, evidence is limited with regards to the array of treatments received by mCRC patients. OBJECTIVE: This study examines treatment sequences (first- to third-line chemotherapy/targeted biologics) and the factors associated with first-line targeted biologics and common treatment sequences for elderly mCRC patients treated in a community setting...
March 2016: Drugs—Real World Outcomes
Tyler Friedrich, Stephen Leong, Christopher H Lieu
Despite numerous breakthroughs in the understanding of colorectal cancer and identification of many oncogenic mutations, the treatment of metastatic colorectal cancer remains relatively more empiric than targeted. Testing for mutations in rat sarcoma virus (RAS) and rapidly growing fibrosarcoma (RAF) are routinely performed, though identification of these mutations currently offers little more than a negative predictive marker for response to EGFR inhibitor treatment and, in the case of RAF mutation, a poor prognostic indicator...
October 2016: Journal of Gastrointestinal Oncology
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