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https://www.readbyqxmd.com/read/28736637/primary-and-acquired-resistance-to-biologic-therapies-in-gastrointestinal-cancers
#1
REVIEW
Sam J Lubner, Nataliya V Uboha, Dustin A Deming
Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736628/predictive-and-prognostic-biomarkers-in-personalized-gastrointestinal-cancer-treatment
#2
REVIEW
Helena Verdaguer, Tamara Saurí, Teresa Macarulla
Biomarkers play an important role in the detection and management of cancer patients. In gastrointestinal cancer, there is increasing interest in their development and validation according to specific tumor type. Prognostic biomarkers enable identification of patients with a more aggressive tumor evolution, while predictive biomarkers permit the identification of patients with a higher probability of responding or not to a specific treatment. Several biomarkers are currently widely employed in gastrointestinal cancers...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736627/personalized-and-precision-medicine-integrating-genomics-into-treatment-decisions-in-gastrointestinal-malignancies
#3
REVIEW
Trang H Au, Kai Wang, David Stenehjem, Ignacio Garrido-Laguna
The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC)...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28728050/topoisomerase-expression-and-amplification-in-solid-tumours-analysis-of-24-262-patients
#4
Gregory M Heestand, Maria Schwaederle, Zoran Gatalica, David Arguello, Razelle Kurzrock
BACKGROUND: Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well. SUMMARY OF METHODS: We analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers...
July 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28712102/precision-medicine-in-metastatic-colorectal-cancer-relevant-carcinogenic-pathways-and-targets-part-2-approaches-beyond-first-line-therapy-and-novel-biologic-agents-under-investigation
#5
REVIEW
Benjamin A Weinberg, Marion L Hartley, Mohamed E Salem
A frequent quandary for oncologists is the selection of chemotherapy and biologic therapy for patients with metastatic colorectal cancer in second-line and higher treatment settings. While not approved by the US Food and Drug Administration (FDA) in the first-line setting, the vascular endothelial growth factor (VEGF)-targeting agents ziv-aflibercept and ramucirumab are appropriate treatment options in the second-line setting, as is continuation of first-line bevacizumab. Tumor RAS mutational status is helpful to determine which patients may benefit from epidermal growth factor receptor (EGFR)-directed therapies, and other novel biomarkers (BRAF, HER2, and mismatch repair deficiency) allow us to select patients who may benefit from biologic therapies that are FDA-approved for other malignancies...
July 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28669023/pooled-analysis-of-clinical-outcome-of-patients-with-chemorefractory-metastatic-colorectal-cancer-treated-within-phase-i-ii-clinical-studies-based-on-individual-biomarkers-of-susceptibility-a-single-institution-experience
#6
Andrea Sartore-Bianchi, Alessio Amatu, Erica Bonazzina, Stefano Stabile, Laura Giannetta, Giulio Cerea, Ilaria Schiavetto, Katia Bencardino, Chiara Funaioli, Riccardo Ricotta, Tiziana Cipani, Michele Schirru, Valentina Gambi, Laura Palmeri, Giulia Carlo-Stella, Francesca Rusconi, Sara Di Bella, Giovanni Burrafato, Andrea Cassingena, Emanuele Valtorta, Calogero Lauricella, Federica Pazzi, Alessandra Gambaro, Silvia Ghezzi, Giovanna Marrapese, Emiliana Tarenzi, Silvio Veronese, Mauro Truini, Angelo Vanzulli, Salvatore Siena
BACKGROUND: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. OBJECTIVE: We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s)...
July 1, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28629479/evaluation-of-invasive-breast-cancer-samples-using-a-12-chemokine-gene-expression-score-correlation-with-clinical-outcomes
#7
Sangeetha Prabhakaran, Victoria T Rizk, Zhenjun Ma, Chia-Ho Cheng, Anders E Berglund, Dominico Coppola, Farah Khalil, James J Mulé, Hatem H Soliman
BACKGROUND: A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center's Total Cancer Care (TCC) patients with non-metastatic breast cancer. METHODS: Affymetrix gene expression profiles were used to interrogate the CS by the principal component method...
June 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28617917/genomic-profiling-of-small-bowel-adenocarcinoma
#8
Alexa B Schrock, Craig E Devoe, Robert McWilliams, James Sun, Thomas Aparicio, Philip J Stephens, Jeffrey S Ross, Richard Wilson, Vincent A Miller, Siraj M Ali, Michael J Overman
Importance: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking. Objective: To perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations. Design, Setting, and Participants: Prospective analysis was performed of clinical samples from patients with SBA (n = 317), colorectal cancer (n = 6353), and gastric carcinoma (n = 889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions...
June 15, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28584889/associations-between-early-tumor-shrinkage-and-depth-of-response-and-clinical-outcomes-in-patients-treated-with-1st-line-chemotherapy-for-advanced-gastric-cancer
#9
Hiroki Osumi, Daisuke Takahari, Eiji Shinozaki, Keisho Chin, Mariko Ogura, Takeru Wakatsuki, Takashi Ichimura, Izuma Nakayama, Tomohiro Matsushima, Kensei Yamaguchi
BACKGROUND: Although early tumor shrinkage (ETS) predictions of the efficacy and depth of response (DpR) reflects clinical outcomes in chemotherapy with epidermal growth factor receptor inhibitor regimens to treat metastatic colorectal cancer, their value in assessing treatments for advanced gastric cancer (AGC) is unclear. Here we evaluated relationships between ETS and DpR and clinical outcomes in AGC patients treated with first-line chemotherapy. METHODS: We retrospectively enrolled 612 consecutive patients treated with first-line chemotherapy for AGC between January 2010 and June 2016...
June 5, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28582279/prevalence-and-influence-on-outcome-of-her2-neu-her3-and-nrg1-expression-in-patients-with-metastatic-colorectal-cancer
#10
Arndt Stahler, Volker Heinemann, Jens Neumann, Alexander Crispin, Andreas Schalhorn, Sebastian Stintzing, Clemens Giessen-Jung, Ludwig Fischer von Weikersthal, Ursula Vehling-Kaiser, Martina Stauch, Detlef Quietzsch, Julian W Holch, Stephan Kruger, Michael Haas, Marlies Michl, Jobst von Einem, Thomas Kirchner, Andreas Jung, Dominik P Modest
Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands' neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low: 192 vs. high: 16), HER2/neu (low: 201 vs. high: 7) and HER3 (low: 69 vs. high: 139) expressions were assessed in 208 patients...
August 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28581874/cost-drivers-for-breast-lung-and-colorectal-cancer-care-in-a-commercially-insured-population-over-a-6-month-episode-an-economic-analysis-from-a-health-plan-perspective
#11
Bhuvana Sagar, Yu Shen Lin, Liana D Castel
AIMS: In the absence of clinical data, accurate identification of cost drivers is needed for economic comparison in an alternate payment model. From a health plan perspective using claims data in a commercial population, the objective was to identify and quantify the effects of cost drivers in economic models of breast, lung, and colorectal cancer costs over a 6-month episode following initial chemotherapy. RESEARCH DESIGN AND METHODS: This study analyzed claims data from 9,748 Cigna beneficiaries with diagnosis of breast, lung, and colorectal cancer following initial chemotherapy from January 1, 2014 to December 31, 2015...
July 3, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#12
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28489607/trans-scirpusin-a-showed-antitumor-effects-via-autophagy-activation-and-apoptosis-induction-of-colorectal-cancer-cells
#13
Eun-Hye Hong, Eun-Young Heo, Jae-Hyoung Song, Bo-Eun Kwon, Jae-Young Lee, Yaejeong Park, Jinwoong Kim, Sun-Young Chang, Young-Won Chin, Sang-Min Jeon, Hyun-Jeong Ko
Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412781/molecular-testing-to-optimize-and-personalize-decision-making-in-the-management-of-colorectal-cancer
#14
REVIEW
Marwan Al-Hajeili, Anthony F Shields, Jimmy J Hwang, Raymond C Wadlow, John L Marshall
Recent improvements in our understanding of the biology of colorectal cancer have led to the identification of several important prognostic and predictive markers of disease-associated risk and treatment response for the individual patient. Proper utilization of these biomarkers can enable physicians to tailor therapeutic strategies to maximize the likelihood of response and minimize treatment toxicity. In the management of colorectal cancer, tremendous progress has been made in the development of strategies for immune checkpoint inhibition; in refinement of agents and approaches used in targeted therapy; and in techniques for molecular subtyping of tumor samples that have identified patient subgroups with clinically relevant cellular differences potentially affecting clinical management and treatment outcome...
April 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28373301/profiling-differential-responses-to-pan-her-inhibition
#15
(no author information available yet)
Findings from the phase II SUMMIT basket trial indicate that among patients with solid cancers harboring HER2/3 mutations, responses to the investigational pan-HER inhibitor neratinib vary by specific alteration and tumor type. Neratinib showed promising single-agent activity in breast, biliary tract, and cervical cancers, but was ineffective against bladder and colorectal cancers; among a small subset of patients with HER3 mutations, no responses were seen.
June 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28366103/methods-of-selecting-combination-therapy-for-colorectal-cancer-patients-a-patent-evaluation-of-us20160025730a1
#16
Daniel Plano, Verónica Alcolea, Carmen Sanmartín, Arun K Sharma
Colorectal cancer (CRC) is the fourth most common cancer worldwide. Targeted therapy drugs (TTDs) are a valid treatment, epithelial growth factor receptor (EGFR) inhibitors being one of the most commonly used for CRC patients. However, this treatment is only useful for patients with wild-type KRAS (wtKRAS) and is effective only on about 40 to 60% of this subset due to the high plasticity of ErbB network. Areas covered: The invention proposes the use of ErbB protein levels and ErbB receptor dimer formation as biomarkers for selecting, predicting and monitoring CRC patients showing sensitivity to the action of EGFR inhibitors to benefit from the combination therapy of EGFR and HER2 inhibitors...
May 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28363756/her2-as-an-emerging-oncotarget-for-colorectal-cancer-treatment-after-failure-of-anti-epidermal-growth-factor-receptor-therapy
#17
REVIEW
Naoki Takegawa, Kimio Yonesaka
Amplification of the HER2 gene is an indicator of poor prognosis for several kinds of malignancies such as breast and gastric cancer, and anti-HER2 targeting therapies provide clinical benefits in these patients. In 2011, HER2 was identified as a resistance molecule for de novo and secondary anti-epidermal growth factor receptor (EGFR) antibody therapy. HER2 activation provides a bypass signaling pathway after anti-EGFR antibody treatment of colorectal cancer. Cell line-based screening revealed that HER2 genomic amplification induces resistance to the anti-EGFR antibody cetuximab in colorectal cancer...
March 9, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28280626/current-companion-diagnostics-in-advanced-colorectal-cancer-getting-a-bigger-and-better-piece-of-the-pie
#18
REVIEW
Jonathan M Loree, Scott Kopetz, Kanwal P S Raghav
While the treatment of colorectal cancer continues to rely heavily on conventional cytotoxic therapy, an increasing number of targeted agents are under development. Many of these treatments require companion diagnostic tests in order to define an appropriate population that will derive benefit. In addition, a growing number of biomarkers provide prognostic information about a patient's malignancy. As we learn more about these biomarkers and their assays, selecting the appropriate companion diagnostic becomes increasingly important...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#19
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28275303/high-levels-of-serum-platelet-derived-growth-factor-aa-and-human-epidermal-growth-factor-receptor-2-are-predictors-of-colorectal-cancer-liver-metastasis
#20
Hong-Da Pan, Yi-Fan Peng, Gang Xiao, Jin Gu
AIM: To develop predictive markers in blood for colorectal cancer liver metastasis. METHODS: Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was IIIC (T3-4N2M0), while another 10 patients with synchronous liver metastasis (TNM stage IV) were recruited for group B. During the surgical procedure, a 10-mL drainage vein (DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV...
February 21, 2017: World Journal of Gastroenterology: WJG
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