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EGFR and colorectal cancer

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https://www.readbyqxmd.com/read/29773991/first-biologic-drug-in-the-treatment-of-ras-wild-type-metastatic-colorectal-cancer-anti-egfr-or-bevacizumab-results-from-a-meta-analysis
#1
REVIEW
Alessandro Ottaiano, Alfonso De Stefano, Monica Capozzi, Anna Nappi, Chiara De Divitiis, Carmela Romano, Lucrezia Silvestro, Antonino Cassata, Rossana Casaretti, Salvatore Tafuto, Michele Caraglia, Massimiliano Berretta, Guglielmo Nasti, Antonio Avallone
Introduction: We performed a meta-analysis in order to analyze and quantify the effect on survival of starting therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC) patients with anti-EGFR agents or bevacizumab. Patients and Methods: Randomized, phase II or III, clinical trials reporting overall survival (OS) in RAS wt mCRC patients treated with first-line chemotherapy (CT) associated with bevacizumab or anti-EGFR agents were selected. The primary end-point of this meta-analysis was OS; findings were depicted in classical Forest plots...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29769385/phase-ii-study-of-irinotecan-plus-panitumumab-as-second-line-therapy-for-patients-with-advanced-esophageal-adenocarcinoma
#2
Harry Yoon, Anita Choudhary, Ramla Kosozi, Gurvinder Singh Bali, Ali Zaidi, Ajlan Atasoy, Arlene A Forastiere, Michael K Gibson
LESSON LEARNED: Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. BACKGROUND: Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29765773/optimising-the-use-of-cetuximab-in-the-continuum-of-care-for-patients-with-metastatic-colorectal-cancer
#3
REVIEW
Richard M Goldberg, Clara Montagut, Zev A Wainberg, Philippe Ronga, François Audhuy, Julien Taieb, Sebastian Stintzing, Salvatore Siena, Daniele Santini
The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line...
2018: ESMO Open
https://www.readbyqxmd.com/read/29764162/the-evolving-role-of-immune-oncology-in-colorectal-cancer
#4
Shaheenah Dawood
Metastatic colorectal cancer still remains an essentially non curable disease. However, with advances in chemotherapeutic and personalizing therapeutic approaches with the incorporation of targeted therapy such as anti-EGFR and anti-VEGF agents survival associated with metastatic colorectal cancer has certainly improved over the last two decades. Patients who are not amenable to surgery median survival remain approximately 2 to 3 years. In an attempt to improve prognostic outcome over the last decade research has focused on therapeutic options geared towards harnessing the immune system with success observed with the use of immune checkpoint inhibitors in the realm of a number of solid tumors including lung and renal cancer...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29760556/rechallenge-of-oxaliplatin-containing-regimens-in-the-third-or-later-line-therapy-for-patients-with-heavily-treated-metastatic-colorectal-cancer
#5
Qiong Yang, Yuanyuan Huang, Zhimin Jiang, Huizhong Wang, Weiyu Li, Bei Zhang, Derong Xie
Purpose: The third- or later-line therapy available often yield poor survival benefit in patients metastatic colorectal cancer (mCRC). The retrospective study aimed to evaluate efficacy of rechallenge of oxaliplatin-containing regimens. Patients and methods: Patients with mCRC who progressed from fluoropyrimidine, oxaliplatin, and irinotecan in the first- and second-line chemotherapy, were treated by reexposure to oxaliplatin-containing regimen. Patients treated by anti-epidermal growth factor receptor (EGFR) antibodies with irinotecan were included in the control arm...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29755687/clinical-application-of-targeted-next-generation-sequencing-for-colorectal-cancer-patients-a-multicentric-belgian-experience
#6
Nicky D'Haene, Quitterie Fontanges, Nancy De Nève, Oriane Blanchard, Barbara Melendez, Monique Delos, Marie-Françoise Dehou, Calliope Maris, Nathalie Nagy, Emmanuel Rousseau, Josse Vandenhove, André Gilles, Carine De Prez, Laurine Verset, Marie-Paule Van Craynest, Pieter Demetter, Jean-Luc Van Laethem, Isabelle Salmon, Marie Le Mercier
International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755130/restoring-puma-induction-overcomes-kras-mediated-resistance-to-anti-egfr-antibodies-in-colorectal-cancer
#7
Kyle Knickelbein, Jingshan Tong, Dongshi Chen, Yi-Jun Wang, Sandra Misale, Alberto Bardelli, Jian Yu, Lin Zhang
Intrinsic and acquired resistance to anti-EGFR antibody therapy, frequently mediated by a mutant or amplified KRAS oncogene, is a significant challenge in the treatment of colorectal cancer (CRC). However, the mechanism of KRAS-mediated therapeutic resistance is not well understood. In this study, we demonstrate that clinically used anti-EGFR antibodies, including cetuximab and panitumumab, induce killing of sensitive CRC cells through p73-dependent transcriptional activation of the pro-apoptotic Bcl-2 family protein PUMA...
May 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29755114/az304-a-novel-dual-braf-inhibitor-exerts-anti-tumour-effects-in-colorectal-cancer-independently-of-braf-genetic-status
#8
Rui Ma, Ling Xu, Xiujuan Qu, Xiaofang Che, Ye Zhang, Yibo Fan, Ce Li, Tianshu Guo, Kezuo Hou, Xuejun Hu, Lisa Drew, Minhui Shen, Tony Cheung, Yunpeng Liu
BACKGROUND: BRAF mutation is associated with poor clinical outcome of patients with malignant tumours, and mediates resistance to chemotherapy and targeted therapy. This study aimed to determine whether V600E mutant and wild type BRAF colorectal cancers exhibit distinct sensitivities to the dual BRAF inhibitor AZ304. METHODS: Kinase activity was assessed by the AlphaScreen assay. Then, MTT assay, EdU assay, colony-formation assay and Western blot were performed to evaluate the anti-tumour effects of AZ304 in vitro...
May 14, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#9
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29752127/implementation-of-next-generation-sequencing-technology-for-somatic-mutation-detection-in-routine-laboratory-practice
#10
Tindaro Giardina, Cleo Robinson, Fabienne Grieu-Iacopetta, Michael Millward, Barry Iacopetta, Dominic Spagnolo, Benhur Amanuel
The introduction of next generation sequencing (NGS) in the routine diagnostic setting is still in the development phase and has been limited by its complexity. Targeted NGS offers an attractive alternative to performing multiple single target assays and is very useful in meeting the increasing clinical demand for testing of multiple genetic aberrations in cancer specimens. To this end, we carried out a blinded validation study on 113 tumours in a diagnostic laboratory and compared mutation results from targeted NGS with those from Sanger sequencing, pyrosequencing, competitive allele specific TaqMan polymerase chain reaction (CAST PCR) and Cobas assays...
May 8, 2018: Pathology
https://www.readbyqxmd.com/read/29745737/the-safety-of-trifluridine-and-tipiracil-for-the-treatment-of-metastatic-colorectal-cancer
#11
Julia Martinez-Perez, M Carmen Riesco-Martinez, Rocio Garcia-Carbonero
TAS102 is an oral thymidine-based nucleoside analogue that has been approved for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) agents and, if RAS wild-type, anti-epidermal growth factor receptor (EGFR) therapy. The pivotal RECOURSE phase III trial demonstrated a significant improvement in disease control rate, progression-free (PFS) and overall survival (OS) as compared with placebo in patients with refractory mCRC...
May 10, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29745070/prognostic-significance-of-egfr-and-cox-2-expression-in-colorectal-cancer-and-their-association-a-study-in-greek-population
#12
Jie Sun, Jingang Zhang
PURPOSE: To identify the sentinel lymph node (SLN) in abdominal lymph node metastases of elderly patients with colorectal cancer using carbon nanoparticles (CN). METHODS: 80 colorectal cancer patients admitted to the affiliated Weihai Second Municipal Hospital of Qingdao University from November 2014 to February 2017 were selected, and divided into the control group (n=40) and the study group (n=40). The control group was treated with surgery, while the study group was administered CN tracer subcutaneously for intraoperative dye positioning; the first to four black-stained lymph nodes were marked as SLN and then radical surgery for CRC followed...
March 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29740957/egfr-exon-20-insertion-mutation-in-advanced-thymic-squamous-cell-carcinoma-response-to-apatinib-and-clinical-outcomes
#13
Su Yudong, Meng Zhaoting, Wang Xinyue, Lin Li, Xu Xiaoyan, Zuo Ran, Chen Jinliang, Chen Peng
Thymic carcinoma (TC) is a rare malignant tumor of the mediastinum with occult onset, rapid development, and poor prognosis. Surgery is the main treatment for early TC, but the majority of patients are diagnosed at Masaoka-Koga stage III or IV with local invasion or distant metastasis. Platinum and anthracyclines are currently considered key components of first-line chemotherapy for advanced TC; however, there are no standard treatment plans for patients who are refractory to first-line and further chemotherapy...
May 8, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29739790/phase-ib-ii-study-of-second-line-therapy-with-panitumumab-irinotecan-and-everolimus-pie-in-kras-wild-type-metastatic-colorectal-cancer
#14
Amanda Townsend, Niall C Tebbutt, Christos S Karapetis, Pamela Cooper, Nimit Singhal, Sue J Yeend, Louise Pirc, Rohit Joshi, Jennifer Elizabeth Hardingham, Timothy Price
PURPOSE: Inhibition of mTOR in addition to EGFR may overcome resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC). This phase Ib/II study evaluated the safety and efficacy of the combination of irinotecan, panitumumab and everolimus. EXPERIMENTAL DESIGN: Patients with KRAS exon 2 WT mCRC following failure of fluoropyrimidine based therapy received IV irinotecan and panitumumab every 2 weeks, and everolimus orally throughout a 14 day cycle. The primary endpoint of the phase II study was response rate (RR)...
May 8, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29737864/panitumumab-in-the-treatment-of-metastatic-colorectal-cancer-including-wild-type-ras-kras-and-nras-mcrc
#15
Mark McGregor, Timothy J Price
The humanized monoclonal antibody panitumumab, targeted against EGFR, plays an important role in patients with metastatic colorectal cancer. This article reviews the body of evidence for panitumumab which demonstrates significant benefits across multiple lines of therapy in those without an extended RAS mutation. The use of panitumumab with RAS mutations is not beneficial and possibly harmful. Panitumumab is well tolerated with manageable toxicities. The role of panitumumab continues to evolve as understanding of sequencing of therapies grows...
May 8, 2018: Future Oncology
https://www.readbyqxmd.com/read/29727211/management-and-grading-of-egfr-inhibitor-induced-cutaneous-toxicity
#16
Janette Beech, Theodora Germetaki, Mary Judge, Nina Paton, Joanne Collins, Abigail Garbutt, Michael Braun, Jill Fenwick, Mark P Saunders
Cutaneous toxicities associated with EGFR inhibitors (EGFRIs) have a significant impact on patient treatment continuation, quality of life and healthcare resource utilization. This paper reviews the current prophylaxis and management of EGFRI-induced cutaneous toxicities in patients with colorectal cancer, and combines these findings with the authors' clinical expertise to define a novel algorithm for healthcare professionals managing patients receiving EGFRIs. This tool includes a grading system based on the location, severity and psychological impact, and provides a standard prescription pack, advice on prophylaxis/self-management of cutaneous symptoms for patients initiating EGFRIs, and essential guidance on subsequent review and treatment escalation...
May 4, 2018: Future Oncology
https://www.readbyqxmd.com/read/29721154/consensus-molecular-subtypes-classification-of-colorectal-cancer-as-a-predictive-factor-for-chemotherapeutic-efficacy-against-metastatic-colorectal-cancer
#17
Akira Okita, Shin Takahashi, Kota Ouchi, Masahiro Inoue, Mika Watanabe, Mareyuki Endo, Hiroshi Honda, Yasuhide Yamada, Chikashi Ishioka
The consensus molecular subtypes (CMS) classification is one of the most robust colorectal cancer (CRC) classifications based on comprehensive gene expression profiles. This study aimed to clarify whether the CMS is a predictive factor for therapeutic effects of standard chemotherapies for metastatic CRC (mCRC). We retrospectively enrolled 193 patients with mCRCs, and using comprehensive gene expression data, classified them into 4 subtypes: CMS1-CMS4. The associations between the subtypes and treatment outcomes were analyzed...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720900/update-on-sporadic-colorectal-cancer-genetics
#18
REVIEW
Karin M Hardiman
Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors...
May 2018: Clinics in Colon and Rectal Surgery
https://www.readbyqxmd.com/read/29703606/final-analysis-of-outcomes-and-ras-braf-status-in-a-randomized-phase-3-study-of-panitumumab-and-best-supportive-care-in-chemorefractory-wild-type-kras-metastatic-colorectal-cancer
#19
Tae Won Kim, Anneli Elme, Joon Oh Park, Anghel Adrian Udrea, Sun Young Kim, Joong Bae Ahn, Ricardo Villalobos Valencia, Srinivasan Krishnan, Nebojsa Manojlovic, Xuesong Guan, Catherine Lofton-Day, A Scott Jung, Eduard Vrdoljak
INTRODUCTION: Tumor rat sarcoma gene (RAS) status is a negative predictive biomarker for anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC). We analyzed outcomes according to RAS and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutational status, and evaluated early tumor shrinkage (ETS) and depth of response (DpR) for patients with wild type RAS. PATIENTS AND METHODS: Patients with confirmed metastatic colon or rectum adenocarcinoma, wild type Kristen rat sarcoma gene tumor exon 2 status, clinical/radiologic disease progression or toxicity during irinotecan or oxaliplatin treatment, and no previous anti-EGFR therapy were randomized 1:1 to receive best supportive care (BSC) with or without panitumumab (6...
March 21, 2018: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29703472/single-cell-coagulomes-as-constituents-of-the-oncogene-driven-coagulant-phenotype-in-brain-tumours
#20
Nadim Tawil, Shilpa Chennakrishnaiah, Rayhaan Bassawon, Radia Johnson, Esterina D'Asti, Janusz Rak
Molecular profiling of human cancers revealed a startling diversity in disease-causing mechanisms superseding histological and anatomical commonalities. The emerging molecular subtypes and disease entities are often driven by distinct oncogenic pathways and their effectors, including those acting extracellularly on the vascular and coagulation systems. Indeed, several oncogenic mutations such as those affecting protein-coding genes (RAS, EGFR, PTEN, TP53) and non-coding RNA (microRNA) regulate multiple effectors of the coagulation system (coagulome), including tissue factor, protease activated receptors, clotting factors, mediators of platelet function and fibrinolysis...
April 2018: Thrombosis Research
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