keyword
MENU ▼
Read by QxMD icon Read
search

EGFR and colorectal cancer

keyword
https://www.readbyqxmd.com/read/28643125/the-role-of-prmt1-in-egfr-methylation-and-signaling-in-mda-mb-468-triple-negative-breast-cancer-cells
#1
Katsuya Nakai, Weiya Xia, Hsin-Wei Liao, Mitsue Saito, Mien-Chie Hung, Hirohito Yamaguchi
BACKGROUND: Epidermal growth factor receptor (EGFR) is often overexpressed in triple-negative breast cancer (TNBC). However, clinical studies have shown that therapies against EGFR are not effective in patients with TNBC. Recently, it has been reported that arginine 198/200 in EGFR extracellular domain is methylated by PRMT1 and that the methylation confers resistance to EGFR monoclonal antibody cetuximab in colorectal cancer cells. To explore a potential mechanism underlying intrinsic resistance to anti-EGFR therapy in TNBC, we investigated the role of PRMT1 in EGFR methylation and signaling in MDA-MB-468 (468) TNBC cells...
June 22, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28639239/significant-improvement-in-detecting-braf-kras-and-egfr-mutations-using-next-generation-sequencing-as-compared-with-fda-cleared-kits
#2
Wanlong Ma, Steven Brodie, Sally Agersborg, Vincent A Funari, Maher Albitar
INTRODUCTION: We compared mutations detected in EGFR, KRAS, and BRAF genes using next-generation sequencing (NGS) and confirmed by Sanger sequencing with mutations that could be detected by FDA-cleared testing kits. METHODS: Paraffin-embedded tissue from 822 patients was tested for mutations in EGFR, KRAS, and BRAF by NGS. Sanger sequencing of hot spots was used with locked nucleic acid to increase sensitivity for specific hot-spot mutations. This included 442 (54%) lung cancers, 168 (20%) colorectal cancers, 29 (4%) brain tumors, 33 (4%) melanomas, 14 (2%) thyroid cancers, and 16% others (pancreas, head and neck, and cancer of unknown origin)...
June 21, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28638266/nuclear-expression-of-gs28-protein-a-novel-biomarker-that-predicts-prognosis-in-colorectal-cancers
#3
Sung Hak Lee, Hyung Jae Yoo, Do Eun Rim, Yinji Cui, Ahwon Lee, Eun Sun Jung, Seung Taek Oh, Jun Gi Kim, Oh-Joo Kwon, Su Young Kim, Seong-Whan Jeong
Aims: GS28 (Golgi SNARE protein, 28 kDa), a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) protein family, plays a critical role in mammalian endoplasmic reticulum (ER)-Golgi or intra-Golgi vesicle transport. To date, few researches on the GS28 protein in human cancer tissues have been reported. In this study, we assessed the prognostic value of GS28 in patients with colorectal cancer (CRC). Methods and results: We screened for GS28 expression using immunohistochemistry in 230 surgical CRC specimens...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28632725/the-role-of-primary-tumour-sidedness-egfr-gene-copy-number-and-egfr-promoter-methylation-in-ras-braf-wild-type-colorectal-cancer-patients-receiving-irinotecan-cetuximab
#4
Laura Demurtas, Marco Puzzoni, Riccardo Giampieri, Pina Ziranu, Valeria Pusceddu, Alessandra Mandolesi, Chiara Cremolini, Gianluca Masi, Fabio Gelsomino, Carlotta Antoniotti, Cristian Loretelli, Fausto Meriggi, Alberto Zaniboni, Alfredo Falcone, Stefano Cascinu, Mario Scartozzi
BACKGROUND: The data from randomised trials suggested that primary tumour sidedness could represent a prognostic and predictive factor in colorectal cancer (CRC) patients, particularly during treatment with anti-epidermal growth factor receptor (EGFR) therapy. However, an in-deep molecular selection might overcome the predictive role of primary tumour location in this setting. METHODS: We conducted a retrospective analysis in which tumour samples from RAS/BRAF wild-type (WT) metastatic CRC patients treated with second-third-line irinotecan/cetuximab were analysed for EGFR gene copy number (GCN) and promoter methylation...
June 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28626084/optimization-of-ras-braf-mutational-analysis-confirms-improvement-in-patient-selection-for-clinical-benefit-to-anti-egfr-treatment-in-metastatic-colorectal-cancer
#5
Cristina Santos, Daniel Azuara, Rocio Garcia-Carbonero, Pilar García Alfonso, Alfredo Carrato, Elena Elez, Auxiliadora Gómez, Ferran Losa, Clara Montagut, Bartomeu Massuti, Valenti Navarro, Mar Varela, Adriana López-Doriga, Victor Moreno, Manuel Valladares, Jose Luis Manzano, José Maria Viéitez, Enrique Aranda, Xavier Sanjuan, Josep Tabernero, Gabriel Capella, Ramon Salazar
In metastatic colorectal cancer (mCRC) recent studies have shown the importance to accurately quantify low-abundance mutations of RAS pathway because anti-EGFR therapy may depend on certain mutation thresholds. We aimed to evaluate the added predictive value of extended RAS panel testing using two commercial assays and a highly sensitive and quantitative digital PCR (dPCR). Tumor samples from 583 mCRC patients treated with anti-EGFR (n=255) or bevacizumab (n=328) based therapies from several clinical trials and retrospective series from the TTD/RTICC Spanish network were analyzed by cobas®, therascreen® and dPCR...
June 16, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28618430/extreme-assay-sensitivity-in-molecular-diagnostics-further-unveils-intratumour-heterogeneity-in-metastatic-colorectal-cancer-as-well-as-artifactual-low-frequency-mutations-in-the-kras-gene
#6
Sara Mariani, Luca Bertero, Simona Osella-Abate, Cristiana Di Bello, Paola Francia di Celle, Vittoria Coppola, Anna Sapino, Paola Cassoni, Caterina Marchiò
BACKGROUND: Gene mutations in the RAS family rule out metastatic colorectal carcinomas (mCRCs) from anti-EGFR therapies. METHODS: We report a retrospective analysis by Sequenom Massarray and fast COLD-PCR followed by Sanger sequencing on 240 mCRCs. RESULTS: By Sequenom, KRAS and NRAS exons 2-3-4 were mutated in 52.9% (127/240) of tumours, while BRAF codon 600 mutations reached 5% (12/240). Fast COLD-PCR found extra mutations at KRAS exon 2 in 15/166 (9%) of samples, previously diagnosed by Sequenom as wild-type or mutated at RAS (exons 3-4) or BRAF genes...
June 15, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28618397/meta-analysis-of-the-mutational-status-of-circulation-tumor-cells-and-paired-primary-tumor-tissues-from-colorectal-cancer-patients
#7
Yong Liu, Stefano Meucci, Liming Sheng, Ulrich Keilholz
As predictive markers for anti-EGFR therapy, KRAS and BRAF mutations are routinely detected in primary and metastatic colorectal cancer (CRC) cells, but seldom in circulating tumor cells (CTCs). Detecting mutations in CTCs could help explain mutational differences between tumor cells at local sites and distant metastases, thereby improving treatment outcomes. Here, we conducted a systematic review and meta-analysis to compare KRAS and BRAF mutations in paired CTCs and primary tumors from CRC patients, to detect any possible discordance...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618197/analysis-of-mutant-allele-fractions-in-driver-genes-in-colorectal-cancer-biological-and-clinical-insights
#8
Rodrigo Dienstmann, Elena Elez, Guillem Argiles, Ignacio Matos, Enrique Sanz-Garcia, Carolina Ortiz, Teresa Macarulla, Jaume Capdevila, Maria Alsina, Tamara Sauri, Helena Verdaguer, Marta Vilaro, Fiorella Ruiz-Pace, Cristina Viaplana, Ariadna Garcia, Stefania Landolfi, Hector G Palmer, Paolo Nuciforo, Jordi Rodon, Ana Vivancos, Josep Tabernero
Sequencing of tumors is now routine and guides personalized cancer therapy. Mutant allele fractions (MAFs, or the 'mutation dose') of a driver gene may reveal the genomic structure of tumors and influence response to targeted therapies. We performed a comprehensive analysis of MAFs of driver alterations in unpaired primary and metastatic colorectal cancer (CRC) at our institution from 2010 to 2015 and studied their potential clinical relevance. Out of 763 CRC samples, 622 had detailed annotation on overall survival in the metastatic setting (OSmet) and 89 received targeted agents matched to KRAS (MEK inhibitors), BRAF (BRAF inhibitors) or PIK3CA mutations (PI3K pathway inhibitors)...
June 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28611205/mouse-pdx-trial-suggests-synergy-of-concurrent-inhibition-of-raf-and-egfr-in-colorectal-cancer-with-braf-or-kras-mutations
#9
Yung-Mae M Yao, Gregory P Donoho, Philip Iversen, Youyan Zhang, Robert D Van Horn, Amelie Forest, Ruslan Novosiadly, Yue Webster, Ebert J Philip, Steven M Bray, Jason C Ting, Amit Aggarwal, James R Henry, Ramon V Tiu, Gregory D Plowman, Sheng-Bin Peng
Purpose: It is to evaluate the anti-tumor efficacy of cetuximab in combination with LSN3074753, an analogue of LY3009120 and pan-RAF inhibitor in 79 colorectal cancer (CRC) patient derived xenograft (PDX) models.<br />Experimental Design: 79 well characterized CRC PDX models were employed to conduct a single mouse per treatment group (n=1) trial.<br />Results: Consistent with clinical results, cetuximab was efficacious in wild type KRAS and BRAF PDX models, with an overall response rate (ORR) of 6...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28611106/a-novel-combination-treatment-targeting-bcl-xl-and-mcl1-for-kras-braf-mutated-and-bcl2l1-amplified-colorectal-cancers
#10
Sung-Yup Cho, Jee Yun Han, Deukchae Na, Wonyoung Kang, Ahra Lee, Jooyoung Kim, Jieun Lee, Seoyeon Min, Jinjoo Kang, Jeesoo Chae, Jong-Il Kim, Hansoo Park, Won-Suk Lee, Charles Lee
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world, and exhibits heterogeneous characteristics in terms of genomic alterations, expression signature and drug responsiveness. Although there have been considerable efforts to classify this disease based on high-throughput sequencing techniques, targeted treatments for specific subgroups has been limited. KRAS and BRAF mutations are prevalent genetic alterations in CRCs, and patients with mutations in either of these genes have a worse prognosis and are resistant to anti-EGFR treatments...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28600480/mir-193a-3p-is-a-key-tumor-suppressor-in-ulcerative-colitis-associated-colon-cancer-and-promotes-carcinogenesis-through-up-regulation-of-il17rd
#11
Joel Pekow, Katherine Meckel, Urszula Dougherty, Yong Huang, Xindi Chen, Anas Almoghrabi, Reba Mustafi, Fatma Ayaloglu-Butun, Zifeng Deng, Haider I Haider, John Hart, David T Rubin, John H Kwon, Marc Bissonnette
Purpose: Patients with ulcerative colitis (UC) are at increased risk for colorectal cancer, although mechanisms underlying neoplastic transformation are poorly understood. We sought to evaluate the role of microRNAs in neoplasia development in this high-risk population.   <p>Experimental Design: Tissue from 12 controls, 9 UC patients without neoplasia, and 11 UC patients with neoplasia was analyzed. miRNA array analysis was performed and select miRNAs assayed by real-time PCR on the discovery cohort and a validation cohort...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28593995/codon-bias-imposes-a-targetable-limitation-on-kras-driven-therapeutic-resistance
#12
Moiez Ali, Erin Kaltenbrun, Grace R Anderson, Sarah Jo Stephens, Sabrina Arena, Alberto Bardelli, Christopher M Counter, Kris C Wood
KRAS mutations drive resistance to targeted therapies, including EGFR inhibitors in colorectal cancer (CRC). Through genetic screens, we unexpectedly find that mutant HRAS, which is rarely found in CRC, is a stronger driver of resistance than mutant KRAS. This difference is ascribed to common codon bias in HRAS, which leads to much higher protein expression, and implies that the inherent poor expression of KRAS due to rare codons must be surmounted during drug resistance. In agreement, we demonstrate that primary resistance to cetuximab is dependent upon both KRAS mutational status and protein expression level, and acquired resistance is often associated with KRAS(Q61) mutations that function even when protein expression is low...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28591715/brca2-egfr-and-ntrk-mutations-in-mismatch-repair-deficient-colorectal-cancers-with-msh2-or-mlh1-mutations
#13
Safoora Deihimi, Avital Lev, Michael Slifker, Elena Shagisultanova, Qifang Xu, Kyungsuk Jung, Namrata Vijayvergia, Eric A Ross, Joanne Xiu, Jeffrey Swensen, Zoran Gatalica, Mark Andrake, Roland L Dunbrack, Wafik S El-Deiry
Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P < 0.0001) in BRCA2. Of 1104 profiled CRCs from a second cohort (COSMIC), MSH2/MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P < 0...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591157/the-impact-of-de-novo-liver-metastasis-on-clinical-outcome-in-patients-with-advanced-non-small-cell-lung-cancer
#14
Yu-Ping Chang, Yu-Mu Chen, Chien-Hao Lai, Chiung-Yu Lin, Wen-Feng Fang, Cherng-Hua Huang, Shau-Hsuan Li, Hung-Chen Chen, Chin-Chou Wang, Meng-Chih Lin
Liver metastasis has been found to affect outcome in prostate cancer and colorectal cancer, but its role in lung cancer is unclear. The current study aimed to evaluate the impact of de novo liver metastasis (DLM) on stage IV non-small cell lung cancer (NSCLC) outcomes and to examine whether tyrosine kinase inhibitors (TKI) reverse poor prognosis in patients with DLM and epidermal growth factor receptor (EGFR)-mutant NSCLC. Among 1392 newly diagnosed NSCLC patients, 490 patients with stage IV disease treated between November 2010 and March 2014 at Kaohsiung Chang Gung Memorial Hospital were included...
2017: PloS One
https://www.readbyqxmd.com/read/28586741/libidibia-ferrea-presents-antiproliferative-apoptotic-and-antioxidant-effects-in-a-colorectal-cancer-cell-line
#15
Andreza Conceição Véras de Aguiar Guerra, Luiz Alberto Lira Soares, Magda Rhayanny Assunção Ferreira, Aurigena Antunes de Araújo, Hugo Alexandre de Oliveira Rocha, Juliana Silva de Medeiros, Rômulo Dos Santos Cavalcante, Raimundo Fernandes de Araújo Júnior
Colorectal cancer is noted for being one of the most frequent of tumors, with expressive morbidity and mortality rates. In new drug discovery, plants stand out as a source capable of yielding safe and high-efficiency products. Well known in Brazilian popular medicine, Libidibia ferrea (Mart. Ex Tul.) L.P. Queiroz var. ferrea (better known as "ironwood" or "jucá"), has been used to treat a wide spectrum of conditions and to prevent cancer. Using methodologies that involved flow cytometry, spectrophotometry and RT-qPCR assays, crude extracts of the fruits of L...
June 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28583095/the-prognostic-significance-of-kras-and-braf-mutation-status-in-korean-colorectal-cancer-patients
#16
Daeyoun David Won, Jae Im Lee, In Kyu Lee, Seong-Taek Oh, Eun Sun Jung, Sung Hak Lee
BACKGROUND: BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients. METHODS: From July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary's Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status...
June 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28580315/coexistence-of-kras-and-braf-mutations-in-colorectal-cancer-a-case-report-supporting-the-concept-of-tumoral-heterogeneity
#17
Pegah Larki, Ehsan Gharib, Mohammad Yaghoob Taleghani, Fatemeh Khorshidi, Ehsan Nazemalhosseini-Mojarad, Hamid Asadzadeh Aghdaei
The detection of KRAS and BRAF mutations is a crucial step for the correct therapeutic approach and predicting the epidermal growth factor receptor (EGFR)-targeted therapy resistance of colorectal carcinomas. The concomitant KRAS and BRAF mutations occur rarely in the colorectal cancers (CRCs) with the prevalence of less than 0.001% of the cases. In patients with KRAS-mutant tumors, BRAF mutations should not regularly be tested unless the patient is participating in a clinical trial enriching for the presence of KRAS or BRAF-mutated tumor...
2017: Cell Journal
https://www.readbyqxmd.com/read/28576857/braf-mutations-as-predictive-biomarker-for-response-to-anti-egfr-monoclonal-antibodies
#18
Emilie M J van Brummelen, Anthonius de Boer, Jos H Beijnen, Jan H M Schellens
Recently, the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) recommended that patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer could be treated with anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab only in absence of Rat-Sarcoma (RAS) mutations. In addition to the previously established biomarker Kirsten rat sarcoma viral oncogene homolog (KRAS) exon 2, cumulative evidence also shows that patients whose tumors harbor KRAS exons 3 or 4 and neuroblastoma rat-sarcoma viral oncogene homolog (NRAS) exons 2, 3, and 4 mutations are found unlikely to benefit from anti-EGFR treatment...
June 2, 2017: Oncologist
https://www.readbyqxmd.com/read/28561063/selective-analysis-of-cancer-cell-intrinsic-transcriptional-traits-defines-novel-clinically-relevant-subtypes-of-colorectal-cancer
#19
Claudio Isella, Francesco Brundu, Sara E Bellomo, Francesco Galimi, Eugenia Zanella, Roberta Porporato, Consalvo Petti, Alessandro Fiori, Francesca Orzan, Rebecca Senetta, Carla Boccaccio, Elisa Ficarra, Luigi Marchionni, Livio Trusolino, Enzo Medico, Andrea Bertotti
Stromal content heavily impacts the transcriptional classification of colorectal cancer (CRC), with clinical and biological implications. Lineage-dependent stromal transcriptional components could therefore dominate over more subtle expression traits inherent to cancer cells. Since in patient-derived xenografts (PDXs) stromal cells of the human tumour are substituted by murine counterparts, here we deploy human-specific expression profiling of CRC PDXs to assess cancer-cell intrinsic transcriptional features...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28560458/epha2-receptor-activation-with-ephrin-a1-ligand-restores-cetuximab-efficacy-in-nras-mutant-colorectal-cancer-cells
#20
Elisabet Cuyàs, Bernardo Queralt, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Javier A Menendez
Patients with wild-type KRAS metastatic colorectal cancer (mCRC) that harbors NRAS activating mutations do not benefit from anti-EGFR therapies. Very little is known about oncogenic NRAS signaling driving mCRC unresponsiveness to the EGFR-directed antibody cetuximab. Using a system of paired NRAS-mutant and wild-type isogenic mCRC cell lines to explore signaling pathways engaged by the common oncogenic NRAS Q61K variant upon challenge with cetuximab, we uncovered an unexpected mechanism of resistance to cetuximab involving dysregulation of the ephrin-A1/EphA2 signaling axis...
May 30, 2017: Oncology Reports
keyword
keyword
19015
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"