EGFR Antagonists in Cancer Treatment
New England Journal of MedicinePublished 12 March 2008
Fortunato Ciardiello, Giampaolo Tortora
Citations2,022
SJR quartileQ1
SJR score19.08
SNIP13.47
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TL;DR
The mechanisms of action of EGFR inhibitors, their anticancer activity, and clinical issues concerning their use in the treatment of patients with cancer are discussed.
Abstract
Functional activation of growth factors and receptors of the epidermal growth factor receptor (EGFR) family occurs in most epithelial-cell cancers, rendering EGFR a target for cancer treatment. This article discusses the mechanisms of action of EGFR inhibitors, their anticancer activity, and clinical issues concerning their use in the treatment of patients with cancer.
Keywords
Medicine
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578 Citations2002Roy S. Herbst, Anne‐Marie Maddox +10 more
Rash and diarrhea, generally mild and tolerable at doses <or= 600 mg/d, were DLTs at 800mg/d (maximum-tolerated dose), and Pharmacokinetic analyses confirmed suitability of once-daily oral dosing.
JNCI Journal of the National Cancer InstituteAdherence to Therapy With Oral Antineoplastic Agents
569 Citations2002Ann H. Partridge
The LancetDifferent strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial
564 Citations2007Michel Seymour, Tim Maughan +13 more
The data challenge the assumption that, in this non-curative setting, maximum tolerable treatment must necessarily be used first-line in patients with advanced colorectal cancer, and suggest the staged approach of initial single-agent treatment upgraded to combination when required is not worse than first- line combination.
PubMedAcquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis.
557 Citations2001Alicia Viloria‐Petit, Tania Crombet +6 more
The results suggest that variants displaying acquired resistance to anti-EGFR antibodies can emerge in vivo and can do so, at least in part, by mechanisms involving the selection of tumor cell subpopulations with increased angiogenic potential.
British Journal of CancerPTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients
538 Citations2007Milo Frattini, Piercarlo Saletti +8 more
It is demonstrated for the first time that the loss of PTEN protein expression is associated with nonresponsiveness to cetuximab.
Journal of Clinical OncologyMolecular and Pathologic Aspects of Endometrial Carcinogenesis
538 Citations2006Jonathan L. Hecht, George L. Mutter
The precursor lesion of type I endometrioid cancer and the role of genetics and estrogen in its progression are defined and the genetic aspects of endometrial carcinogenesis and progression are reviewed.
Journal of Clinical OncologyMulticenter Phase II and Translational Study of Cetuximab in Metastatic Colorectal Carcinoma Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidines
537 Citations2006Heinz‐Josef Lenz, Eric Van Cutsem +11 more
Cetuximab is active and well tolerated in metastatic CRC refractory to irinotecan, oxaliplatin, and fluoropyrimidines and neither EGFR kinase domain mutations nor EGFR gene amplification appear to be essential for response to cetUXimab in this setting.
Cancer CellBlocking Neuropilin-1 Function Has an Additive Effect with Anti-VEGF to Inhibit Tumor Growth
531 Citations2007Qi Pan, Yvan H. Chanthery +18 more
It is proposed that blocking NRP1 function inhibits vascular remodeling, rendering vessels more susceptible to anti-VEGF therapy, and generated two monoclonal antibodies that bind to the Sema- and VEGF-binding domains of N RP1.
PubMedInsulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling.
513 Citations2002Arnab Chakravarti, Jay S. Loeffler +1 more
Findings suggest that IGFR-I signaling through phosphoinositide 3-kinase may represent a novel and potentially important mechanism of resistance to anti-EGFR therapy.
Journal of Clinical OncologyPhase II Multicenter Study of the Antiepidermal Growth Factor Receptor Monoclonal Antibody Cetuximab in Combination With Platinum-Based Chemotherapy in Patients With Platinum-Refractory Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
491 Citations2005José Baselga, José Trigo +8 more
The combination of cetuximab and platinum chemotherapy is an active and well-tolerated approach to the treatment of this poor-prognosis patient population with platinum-refractory recurrent or metastatic SCCHN for whom there are no recommended standard therapeutic options.
Journal of Clinical OncologyCetuximab, a Monoclonal Antibody Targeting the Epidermal Growth Factor Receptor, in Combination With Gemcitabine for Advanced Pancreatic Cancer: A Multicenter Phase II Trial
482 Citations2004Henry Q. Xiong, Arthur Rosenberg +6 more
Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer.
PubMedIncidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung.
464 Citations1988Sjoerd Rodenhuis, Robbert J.C. Slebos +6 more
It is concluded that mutational K-ras activation is present in about a third of adenocarcinomas of the lung and that the mutational event may be a direct result of one or more carcinogenic ingredients of tobacco smoke.
Cancer ResearchPIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab
462 Citations2008Minaxi Jhawer, Sanjay Goel +11 more
A priori screening of colon tumors for PTEN expression status and PIK3CA and Ras/BRAF mutation status could help stratify patients likely to benefit from this therapy.
OncogeneLoss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors
452 Citations2003Roberto Bianco, Incheol Shin +8 more
Combined blockade of the EGFR tyrosine kinase and Akt should be considered as a therapeutic approach in EGFR-expressing tumor cells with concomitant amplification(s) of PI3K-Akt signaling.
The Journal of UrologyGrowth Inhibition of Human Tumor Cells in Athymic Mice by Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies
448 Citations1984Hideo Masui, Tomoyuki Kawamoto +4 more
The observation that MoAb against the receptor for EGF is cytostatic rather than cytocidal in vitro against A431 cells, yet completely prevents tumor growth in vivo, suggests that some host animal responses also may be involved in the antitumor effect.
CancerCigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung
444 Citations2001Steven A. Ahrendt, P. Decker +8 more
K‐ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender.
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