keyword
MENU ▼
Read by QxMD icon Read
search

EGFR Resistance Colon Cancer

keyword
https://www.readbyqxmd.com/read/29665843/next-generation-sequencing-analysis-of-receptor-type-tyrosine-kinase-genes-in-surgically-resected-colon-cancer-identification-of-gain-of-function-mutations-in-the-ret-proto-oncogene
#1
Duarte Mendes Oliveira, Katia Grillone, Chiara Mignogna, Valentina De Falco, Carmelo Laudanna, Flavia Biamonte, Rosa Locane, Francesco Corcione, Massimiliano Fabozzi, Rosario Sacco, Giuseppe Viglietto, Donatella Malanga, Antonia Rizzuto
BACKGROUND: Improvement in genetic characterization of Colon Cancer (CC) patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are receptor tyrosine kinases (RTKs) whose role in CC need to be better investigated. METHODS: We have analysed 37 CC patients using the Ion AmpliSeq™ Comprehensive Cancer Panel (CCP)...
April 17, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29593231/metabolomic-approach-for-a-rapid-identification-of-natural-products-with-cytotoxic-activity-against-human-colorectal-cancer-cells
#2
Vittoria Graziani, Monica Scognamiglio, Valentina Belli, Assunta Esposito, Brigida D'Abrosca, Angela Chambery, Rosita Russo, Marta Panella, Aniello Russo, Fortunato Ciardiello, Teresa Troiani, Nicoletta Potenza, Antonio Fiorentino
The discovery of bioactive compounds from natural sources entails an extremely lengthy process due to the timescale and complexity of traditional methodologies. In our study, we used a rapid NMR based metabolomic approach as tool to identify secondary metabolites with anti-proliferative activity against a panel of human colorectal cancer cell lines with different mutation profiles. For this purpose, fourteen Fabaceae species of Mediterranean vegetation were investigated using a double screening method:1 H NMR profiling enabled the identification of the main compounds present in the mixtures, whilst parallel biological assays allowed the selection of two plant extracts based on their strong anti-proliferative properties...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29580164/emergence-of-kras-mutation-in-liver-metastases-after-an-anti-egfr-treatment-in-patient-with-colorectal-cancer-are-we-aware-of-the-therapeutic-impact-of-intratumor-heterogeneity
#3
M Baretti, N Personeni, A Destro, A Santoro, L Rimassa
Tumors represent a dynamic system where the genomic plasticity permits to adapt to the perturbation induced by environmental pressures, supporting the importance of longitudinal tumor sampling strategies to deciphering the temporal acquisition of driver event that could impact treatment outcome. We describe the case of a metastatic colorectal cancer (mCRC) patient, RAS wild-type, who responded to anti-EGFR therapy and underwent liver surgery, revealing a KRAS mutations in the metastatic lesion, not detectable prior to initiation of therapy in the colonic biopsy...
March 26, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29498789/impairment-of-k-ras-signaling-networks-and-increased-efficacy-of-egfr-inhibitors-by-a-novel-synthetic-mir-143
#4
Yukihiro Akao, Minami Kumasaki, Haruka Shinohara, Nobuhiko Sugito, Yuki Kuranaga, Takuya Tsujino, Yuki Yoshikawa, Yukio Kitade
Despite considerable research on K-Ras inhibitors, none had been developed until now. We synthesized nuclease-resistant synthetic miR-143 (miR-143#12), which strongly silenced K-Ras, its effector signal molecules AKT and ERKs, and the K-Ras activator Sos1. We examined the anti-proliferative effect of miR-143#12 and the mechanism in human colon cancer DLD-1 cell (G13D) and other cell types harboring K-Ras mutations. Cell growth was markedly suppressed in a concentration-dependent manner by miR-143#12 (IC50 : 1...
March 2, 2018: Cancer Science
https://www.readbyqxmd.com/read/29366445/clinical-implications-of-the-hippo-yap-pathway-in-multiple-cancer-contexts
#5
Han-Byul Kim, Seung-Jae Myung
The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy...
March 2018: BMB Reports
https://www.readbyqxmd.com/read/29312543/dual-targeting-of-her3-and-mek-may-overcome-her3-dependent-drug-resistance-of-colon-cancers
#6
Giulia Bon, Rossella Loria, Carla Azzurra Amoreo, Alessandra Verdina, Isabella Sperduti, Arianna Mastrofrancesco, Silvia Soddu, Maria Grazia Diodoro, Marcella Mottolese, Matilde Todaro, Giorgio Stassi, Michele Milella, Ruggero De Maria, Rita Falcioni
Although the medical treatment of colorectal cancer has evolved greatly in the last years, a significant portion of early-stage patients develops recurrence after therapies. The current clinical trials are directed to evaluate new drug combinations and treatment schedules. By the use of patient-derived or established colon cancer cell lines, we found that the tyrosine kinase receptor HER3 is involved in the mechanisms of resistance to therapies. In agreement, the immunohistochemical analysis of total and phospho-HER3 expression in 185 colorectal cancer specimens revealed a significant correlation with lower disease-free survival...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29167314/wnt-%C3%AE-catenin-pathway-activation-mediates-adaptive-resistance-to-braf-inhibition-in-colorectal-cancer
#7
Guangming Chen, Chenxi Gao, Xuan Gao, Dennis Han Zhang, Shih-Fan Kuan, Timothy F Burns, Jing Hu
One of the most encouraging developments in oncology has been the success of BRAF inhibitors in BRAF-mutant melanoma. However, in contrast to its striking efficacy in BRAF-mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF-mutant colorectal cancer (CRC). While many studies on BRAF inhibitor resistance in CRC have focused on mechanisms underlying the reactivation of the EGFR/RAS/RAF/MEK/ERK pathway, the current study focuses on identifying novel adaptive signaling mechanisms, a fresh angle on CRC resistance to BRAF inhibition...
November 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29061656/synergistic-antiproliferative-activity-of-the-rad51-inhibitor-ibr2-with-inhibitors-of-receptor-tyrosine-kinases-and-microtubule-protein
#8
Peter J Ferguson, Mark D Vincent, James Koropatnick
Although cancer cell genetic instability contributes to characteristics that mediate tumorigenicity, it also contributes to the tumor-selective toxicity of some chemotherapy drugs. This synthetic lethality can be enhanced by inhibitors of DNA repair. To exploit this potential Achilles heel, we tested the ability of a RAD51 inhibitor to potentiate the cytotoxicity of chemotherapy drugs. 2-(Benzylsulfonyl)-1-(1 H -indol-3-yl)-1,2-dihydroisoquinoline (IBR2) inhibits RAD51-mediated DNA double-strand break repair but also enhances cytotoxicity of the Bcr-Abl inhibitor imatinib...
January 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28974546/a-molecularly-annotated-model-of-patient-derived-colon-cancer-stem-like-cells-to-assess-genetic-and-nongenetic-mechanisms-of-resistance-to-anti-egfr-therapy
#9
Paolo Luraghi, Viola Bigatto, Elia Cipriano, Gigliola Reato, Francesca Orzan, Francesco Sassi, Francesca De Bacco, Claudio Isella, Sara E Bellomo, Enzo Medico, Paolo M Comoglio, Andrea Bertotti, Livio Trusolino, Carla Boccaccio
Purpose: Patient-derived xenografts ("xenopatients") of colorectal cancer metastases have been essential to identify genetic determinants of resistance to the anti-EGFR antibody cetuximab and to explore new therapeutic strategies. From xenopatients, a genetically annotated collection of stem-like cultures ("xenospheres") was generated and characterized for response to targeted therapies.Experimental Design: Xenospheres underwent exome-sequencing analysis, gene expression profile, and in vitro targeted treatments to assess genetic, biological, and pharmacologic correspondence with xenopatients, and to investigate nongenetic biomarkers of therapeutic resistance...
October 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28951457/mechanisms-of-acquired-resistance-to-braf-v600e-inhibition-in-colon-cancers-converge-on-raf-dimerization-and-are-sensitive-to-its-inhibition
#10
Rona Yaeger, Zhan Yao, David M Hyman, Jaclyn F Hechtman, Efsevia Vakiani, HuiYong Zhao, Wenjing Su, Lu Wang, Andrew Joelson, Andrea Cercek, Jose Baselga, Elisa de Stanchina, Leonard Saltz, Michael F Berger, David B Solit, Neal Rosen
BRAF V600E colorectal cancers are insensitive to RAF inhibitor monotherapy due to feedback reactivation of receptor tyrosine kinase signaling. Combined RAF and EGFR inhibition exerts a therapeutic effect, but resistance invariably develops through undefined mechanisms. In this study, we determined that colorectal cancer progression specimens invariably harbored lesions in elements of the RAS-RAF-MEK-ERK pathway. Genetic amplification of wild-type RAS was a recurrent mechanism of resistance in colorectal cancer patients that was not seen in similarly resistant melanomas...
December 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28759045/tumor-microenvironment-confers-mtor-inhibitor-resistance-in-invasive-intestinal-adenocarcinoma
#11
T Fujishita, Y Kojima, R Kajino-Sakamoto, M M Taketo, M Aoki
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is frequently activated in cancers and can be counteracted with the clinical mTORC1 inhibitors everolimus and temsirolimus. Although mTORC1 and dual mTORC1/2 inhibitors are currently under development to treat various malignancies, the emergence of drug resistance has proven to be a major complication. Using the cis-Apc/Smad4 mouse model of locally invasive intestinal adenocarcinoma, we show that administration of everolimus or the dual mTORC1/2 inhibitor AZD8055 significantly reduces the growth of intestinal tumors...
November 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28754471/how-to-train-your-inhibitor-design-strategies-to-overcome-resistance-to-epidermal-growth-factor-receptor-inhibitors
#12
REVIEW
Sandra N Milik, Deena S Lasheen, Rabah A T Serya, Khaled A M Abouzid
Epidermal Growth Factor Receptor (EGFR) stands out as a key player in the development of many cancers. Its dysregulation is associated with a vast number of tumors such as non-small-cell lung cancer, colon cancer, head-and-neck cancer, breast and ovarian cancer. Being implicated in the development of a number of the most lethal cancers worldwide, EGFR has long been considered as a focal target for cancer therapies, ever since the FDA approval of "Gefitinib" in 2003 and up to the last FDA approved small molecule EGFR kinase inhibitor "Osimertinib" in 2015...
December 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28736637/primary-and-acquired-resistance-to-biologic-therapies-in-gastrointestinal-cancers
#13
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/28685087/heterogeneity-in-the-colorectal-primary-tumor-and-the-synchronous-resected-liver-metastases-prior-to-and-after-treatment-with-an-anti-egfr-monoclonal-antibody
#14
Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28580315/coexistence-of-kras-and-braf-mutations-in-colorectal-cancer-a-case-report-supporting-the-concept-of-tumoral-heterogeneity
#15
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/28408243/erlotinib-and-bevacizumab-in-patients-with-advanced-non-small-cell-lung-cancer-and-activating-egfr-mutations-belief-an-international-multicentre-single-arm-phase-2-trial
#16
MULTICENTER STUDY
Rafael Rosell, Urania Dafni, Enriqueta Felip, Alessandra Curioni-Fontecedro, Oliver Gautschi, Solange Peters, Bartomeu Massutí, Ramon Palmero, Santiago Ponce Aix, Enric Carcereny, Martin Früh, Miklos Pless, Sanjay Popat, Athanasios Kotsakis, Sinead Cuffe, Paolo Bidoli, Adolfo Favaretto, Patrizia Froesch, Noemí Reguart, Javier Puente, Linda Coate, Fabrice Barlesi, Daniel Rauch, Michael Thomas, Carlos Camps, Jose Gómez-Codina, Margarita Majem, Rut Porta, Riyaz Shah, Emer Hanrahan, Roswitha Kammler, Barbara Ruepp, Manuela Rabaglio, Marie Kassapian, Niki Karachaliou, Rachel Tam, David S Shames, Miguel A Molina-Vila, Rolf A Stahel
BACKGROUND: The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation...
May 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28404754/therapeutic-response-of-metastatic-colorectal-cancer-harboring-a-kras-missense-mutation-after-combination-chemotherapy-with-the-egfr-inhibitor-panitumumab
#17
Emil Lou, Donna D'Souza, Andrew C Nelson
Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the past few years, the scope of tested variants in the KRAS oncogene has expanded significantly, and testing of all RAS family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with KRAS-mutated tumors...
April 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#18
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#19
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28133136/-a-case-of-metastatic-colon-cancer-dramatically-affected-by-anti-egfr-antibody-therapy
#20
Ryoma Yagi, Yoshifumi Shimada, Kohei Miura, Yosuke Tajima, Takuma Okamura, Masato Nakano, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii
RAS mutation is an established predictive biomarker of resistance to anti-epidermal growth factor receptor(EGFR)therapy in metastatic colorectal cancer. In addition, previous studies identified mutations in ERBB2, FGFR1, PDGFRA, BRAF, MAP2K1, PTEN, and PIK3CA as potential mechanisms of resistance to anti-EGFR therapy. Testing for these mutations might be necessary to determine eligibility for anti-EGFR therapy in patients with metastatic colorectal cancer. CancerPlex®is a nextgeneration sequencer for 413 cancer genes...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
keyword
keyword
101904
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"