Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.


:Overexpression of epidermal growth factor receptors (EGFR) occurs in >90% of pancreatic ductal adenocarcinomas (PDACs) and is associated with a poorer prognosis. A systematic review of electronic databases identified studies exploring the addition of EGFR-targeted treatment to chemotherapy in patients with locally advanced (LA)/metastatic PDAC. Efficacy, safety and tolerability of EGFR-targeted therapy were explored using meta-analysis of randomised controlled trials (RCTs). Meta-regression was utilised to explore factors associated with improved prognosis (all studies) and benefit from EGFR-targeted therapy (RCTs). Twenty-eight studies (7 RCTs and 21 cohort studies) comprising 3718 patients were included. The addition of EGFR-targeted treatment to chemotherapy did not improve progression-free (pooled hazard ratio (HR): 0.90, p = 0.15) or overall survival (HR: 0.94, p = 0.18). EGFR-targeted therapy was associated with increased treatment-related deaths (pooled odds ratio (OR): 5.18, p = 0.007), and grade (G)3/4 rash (OR: 4.82, p = 0.03). There was a borderline significant increase in G3/4 diarrhoea (OR: 1.75, p = 0.06), but no effect on treatment discontinuation without progression (OR: 0.87, p = 0.25). Neither G3/4 rash nor diarrhoea were associated with increased survival benefit from EGFR-targeted therapy. The effect of EGFR-targeted therapy on overall survival (OS) appeared greater in studies with a greater proportion of LA rather than metastatic patients (R = -0.69, p < 0.001). Further studies in unselected patients with advanced PDAC are not warranted. The benefit from EGFR inhibitors may be limited to patient subgroups not yet clearly defined.


Int J Mol Sci


Chiramel J,Backen AC,Pihlak R,Lamarca A,Frizziero M,Tariq NU,Hubner RA,Valle JW,Amir E,McNamara MG




Has Abstract


2017-04-26 00:00:00










  • The Immunogenicity of Colorectal Cancer in Relation to Tumor Development and Treatment.

    abstract::Although most cancer types have been viewed as immunologically silent until recently, it has become increasingly clear that the immune system plays key roles in the course of tumor development. Remarkable progress towards understanding cancer immunogenicity and tumor-immune system interactions has revealed important i...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: de Vries NL,Swets M,Vahrmeijer AL,Hokland M,Kuppen PJ

    更新日期:2016-06-29 00:00:00

  • The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease.

    abstract::The mammalian HSP90 family of proteins is a cluster of highly conserved molecules that are involved in myriad cellular processes. Their distribution in various cellular compartments underlines their essential roles in cellular homeostasis. HSP90 and its co-chaperones orchestrate crucial physiological processes such as...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Hoter A,El-Sabban ME,Naim HY

    更新日期:2018-08-29 00:00:00

  • Suppression of SHROOM1 Improves In Vitro and In Vivo Gene Integration by Promoting Homology-Directed Repair.

    abstract::Homologous recombination (HR) is often used to achieve targeted gene integration because of its higher precision and operability compared with microhomology-mediated end-joining (MMEJ) or non-homologous end-joining (NHEJ). It appears to be inefficient for gene integration in animal cells and embryos due to occurring o...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Zhao Z,Zhang H,Xiong T,Wang J,Yang D,Zhu D,Li J,Yang Y,Sun C,Zhao Y,Xi JJ

    更新日期:2020-08-13 00:00:00

  • Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome.

    abstract::Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine kinase that phosphorylates and activates the apoptotic program through interaction with diverse downstream targets including tumor suppressor p53. HIPK2 is activated by genotoxic stimuli and modulates cell fate following DNA damage. The DNA damage ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Kuwano Y,Nishida K,Akaike Y,Kurokawa K,Nishikawa T,Masuda K,Rokutan K

    更新日期:2016-09-27 00:00:00

  • Downhill, Ultrafast and Fast Folding Proteins Revised.

    abstract::Research on the protein folding problem differentiates the protein folding process with respect to the duration of this process. The current structure encoded in sequence dogma seems to be clearly justified, especially in the case of proteins referred to as fast-folding, ultra-fast-folding or downhill. In the present ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Banach M,Stapor K,Konieczny L,Fabian P,Roterman I

    更新日期:2020-10-15 00:00:00

  • Total phenolic contents and antioxidant capacities of herbal and tea infusions.

    abstract::In order to supply new information on the antioxidant function of selected beverages for nutritionists and the general public, total phenolic contents of 51 kinds of herbal and tea infusions made in China were measured by the Folin-Ciocalteu method, and their antioxidant capacities were evaluated using ferric reducing...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Fu L,Xu BT,Gan RY,Zhang Y,Xu XR,Xia EQ,Li HB

    更新日期:2011-01-01 00:00:00

  • Role of Hedgehog Signaling in Vasculature Development, Differentiation, and Maintenance.

    abstract::The role of Hedgehog (Hh) signaling in vascular biology has first been highlighted in embryos by Pepicelli et al. in 1998 and Rowitch et al. in 1999. Since then, the proangiogenic role of the Hh ligands has been confirmed in adults, especially under pathologic conditions. More recently, the Hh signaling has been propo...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Chapouly C,Guimbal S,Hollier PL,Renault MA

    更新日期:2019-06-24 00:00:00

  • The Janus Role of Adhesion in Chondrogenesis.

    abstract::Tackling the first stages of the chondrogenic commitment is essential to drive chondrogenic differentiation to healthy hyaline cartilage and minimize hypertrophy. During chondrogenesis, the extracellular matrix continuously evolves, adapting to the tissue adhesive requirements at each stage. Here, we take advantage of...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Casanellas I,Lagunas A,Vida Y,Pérez-Inestrosa E,Andrades JA,Becerra J,Samitier J

    更新日期:2020-07-24 00:00:00

  • Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion.

    abstract::Retinoids exert antitumor effects through the retinoic acid receptor α (RARα). In the present study, we sought to identify the factors involved in the RARα-mediated transcriptional regulation of the tumor suppressor gene and the tissue factor pathway inhibitor 2 (TFPI2) in hepatocellular carcinoma (H...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Tsuchiya H,Oura S

    更新日期:2018-05-13 00:00:00

  • Applications of Alternative Nucleases in the Age of CRISPR/Cas9.

    abstract::Breakthroughs in the development of programmable site-specific nucleases, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases (MNs), and most recently, the clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (including Cas9)...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Guha TK,Edgell DR

    更新日期:2017-11-29 00:00:00

  • A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level⁻Does hCG Render the Endometrium of RIF Patients?

    abstract:BACKGROUND:The molecular signature of endometrial receptivity still remains barely understood, especially when focused on the possible benefit of therapeutical interventions and implantation-related pathologies. Therefore, the protein composition of tissue and isolated primary cells (endometrial stromal cells, ESCs) fr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Bielfeld AP,Pour SJ,Poschmann G,Stühler K,Krüssel JS,Baston-Büst DM

    更新日期:2019-01-19 00:00:00

  • Explaining the Microtubule Energy Balance: Contributions Due to Dipole Moments, Charges, van der Waals and Solvation Energy.

    abstract::Microtubules are the main components of mitotic spindles, and are the pillars of the cellular cytoskeleton. They perform most of their cellular functions by virtue of their unique dynamic instability processes which alternate between polymerization and depolymerization phases. This in turn is driven by a precise balan...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Ayoub AT,Staelens M,Prunotto A,Deriu MA,Danani A,Klobukowski M,Tuszynski JA

    更新日期:2017-09-22 00:00:00

  • FACS-Based Proteomics Enables Profiling of Proteins in Rare Cell Populations.

    abstract::Understanding disease pathology often does not require an overall proteomic analysis of clinical samples but rather the analysis of different, often rare, subpopulations of cells in a heterogeneous mixture of cell types. For the isolation of pre-specified cellular subtypes, fluorescence activated cell sorting (FACS) i...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Maes E,Cools N,Willems H,Baggerman G

    更新日期:2020-09-08 00:00:00

  • Role of Oxidative Stress in Drug-Induced Kidney Injury.

    abstract::The kidney plays a primary role in maintaining homeostasis and detoxification of numerous hydrophilic xenobiotics as well as endogenous compounds. Because the kidney is exposed to a larger proportion and higher concentration of drugs and toxins than other organs through the secretion of ionic drugs by tubular organic ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Hosohata K

    更新日期:2016-11-01 00:00:00

  • AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    abstract::The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Lei M,Li ZY,Wang JB,Fu YL,Ao MF,Xu L

    更新日期:2016-02-27 00:00:00

  • Effect of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in patients with colorectal cancer.

    abstract::It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Santos JC,Funck A,Silva-Fernandes IJ,Rabenhorst SH,Martinez CA,Ribeiro ML

    更新日期:2014-09-29 00:00:00

  • STVNa Attenuates Isoproterenol-Induced Cardiac Hypertrophy Response through the HDAC4 and Prdx2/ROS/Trx1 Pathways.

    abstract::Recent data show that cardiac hypertrophy contributes substantially to the overall heart failure burden. Mitochondrial dysfunction is a common feature of cardiac hypertrophy. Recent studies have reported that isosteviol inhibits myocardial ischemia-reperfusion injury in guinea pigs and H9c2 cells. This work investigat...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Liu F,Su H,Liu B,Mei Y,Ke Q,Sun X,Tan W

    更新日期:2020-01-20 00:00:00

  • SATB1-Mediated Upregulation of the Oncogenic Receptor Tyrosine Kinase HER3 Antagonizes MET Inhibition in Gastric Cancer Cells.

    abstract::MET-amplified gastric cancer cells are extremely sensitive to MET inhibition in vitro, whereas clinical efficacy of MET inhibitors is disappointing. The compensatory activation of other oncogenic growth factor receptors may serve as an underlying mechanism of resistance. In this study, we analyzed the role of HER rece...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Jenke R,Holzhäuser-Rein M,Mueller-Wilke S,Lordick F,Aigner A,Büch T

    更新日期:2020-12-23 00:00:00

  • Quinacrine-Mediated Inhibition of Nrf2 Reverses Hypoxia-Induced 5-Fluorouracil Resistance in Colorectal Cancer.

    abstract::5-Fluorouracil (5-FU) is an important chemotherapeutic agent for the systemic treatment of colorectal cancer (CRC), but its effectiveness against CRC is limited by increased 5-FU resistance caused by the hypoxic tumor microenvironment. The purpose of our study was to assess the feasibility of using quinacrine (QC) to ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Kim HG,Kim CW,Lee DH,Lee JS,Oh ET,Park HJ

    更新日期:2019-09-05 00:00:00

  • Improving protein crystal quality by the without-oil microbatch method: crystallization and preliminary X-ray diffraction analysis of glutathione synthetase from Pseudoalteromonas haloplanktis.

    abstract::Glutathione synthetases catalyze the ATP-dependent synthesis of glutathione from l-γ-glutamyl- l-cysteine and glycine. Although these enzymes have been sequenced and characterized from a variety of biological sources, their exact catalytic mechanism is not fully understood and nothing is known about their adaptation a...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Merlino A,Russo Krauss I,Albino A,Pica A,Vergara A,Masullo M,De Vendittis E,Sica F

    更新日期:2011-01-01 00:00:00

  • Distribution of alpha thalassaemia gene variants in diverse ethnic populations in malaysia: data from the institute for medical research.

    abstract::Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this r...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Ahmad R,Saleem M,Aloysious NS,Yelumalai P,Mohamed N,Hassan S

    更新日期:2013-09-10 00:00:00

  • Causative Links between Protein Aggregation and Oxidative Stress: A Review.

    abstract::Compelling evidence supports a tight link between oxidative stress and protein aggregation processes, which are noticeably involved in the development of proteinopathies, such as Alzheimer's disease, Parkinson's disease, and prion disease. The literature is tremendously rich in studies that establish a functional link...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Lévy E,El Banna N,Baïlle D,Heneman-Masurel A,Truchet S,Rezaei H,Huang ME,Béringue V,Martin D,Vernis L

    更新日期:2019-08-09 00:00:00

  • Hormonal Responses to Plasmodiophora brassicae Infection in Brassica napus Cultivars Differing in Their Pathogen Resistance.

    abstract::Hormonal dynamics after Plasmodiophora brassicae infection were compared in two Brassica napus cultivars-more resistant SY Alister and more sensitive Hornet, in order to elucidate responses associated with efficient defense. Both cultivars responded to infection by the early transient elevation of active cytokinins (p...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Prerostova S,Dobrev PI,Konradyova V,Knirsch V,Gaudinova A,Kramna B,Kazda J,Ludwig-Müller J,Vankova R

    更新日期:2018-12-13 00:00:00

  • Temporomandibular Joint Regenerative Medicine.

    abstract::The temporomandibular joint (TMJ) is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Van Bellinghen X,Idoux-Gillet Y,Pugliano M,Strub M,Bornert F,Clauss F,Schwinté P,Keller L,Benkirane-Jessel N,Kuchler-Bopp S,Lutz JC,Fioretti F

    更新日期:2018-02-02 00:00:00

  • Reaction with Proteins of a Five-Coordinate Platinum(II) Compound.

    abstract::Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-d...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Ferraro G,Marzo T,Cucciolito ME,Ruffo F,Messori L,Merlino A

    更新日期:2019-01-26 00:00:00

  • Potential Hepatotoxins Found in Herbal Medicinal Products: A Systematic Review.

    abstract::The risk of liver injury associated with the use of herbal medicinal products (HMPs) is well known among physicians caring for patients under a HMP therapy, as documented in case reports or case series and evidenced by using the Roussel Uclaf Causality Assessment Method (RUCAM) to verify a causal relationship. In many...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Quan NV,Dang Xuan T,Teschke R

    更新日期:2020-07-16 00:00:00

  • Antibodies Against the C-Terminus of ApoA-1 Are Inversely Associated with Cholesterol Efflux Capacity and HDL Metabolism in Subjects with and without Type 2 Diabetes Mellitus.

    abstract:BACKGROUND:We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) with anti-c-terminus apoA-1 (Ac-terAA1) and anti-apolipoprotein (apo)-1 (AAA1) autoantibodies in subjects with and without Type 2 diabetes mellitus (T2D). METHODS:In...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Dullaart RPF,Pagano S,Perton FG,Vuilleumier N

    更新日期:2019-02-09 00:00:00

  • Adipose Tissue and Brain Metabolic Responses to Western Diet-Is There a Similarity between the Two?

    abstract::Dietary fats and sugars were identified as risk factors for overweight and neurodegeneration, especially in middle-age, an earlier stage of the aging process. Therefore, our aim was to study the metabolic response of both white adipose tissue and brain in middle aged rats fed a typical Western diet (high in saturated ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Mazzoli A,Spagnuolo MS,Gatto C,Nazzaro M,Cancelliere R,Crescenzo R,Iossa S,Cigliano L

    更新日期:2020-01-25 00:00:00

  • Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against Drug-Resistant Acinetobacter baumannii.

    abstract::Antimicrobial peptides (AMPs) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. Previous studies showed that magainin 2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. The present study was conducted ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Kim MK,Kang N,Ko SJ,Park J,Park E,Shin DW,Kim SH,Lee SA,Lee JI,Lee SH,Ha EG,Jeon SH,Park Y

    更新日期:2018-10-05 00:00:00

  • Competing Endogenous RNA Networks as Biomarkers in Neurodegenerative Diseases.

    abstract::Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Moreno-García L,López-Royo T,Calvo AC,Toivonen JM,de la Torre M,Moreno-Martínez L,Molina N,Aparicio P,Zaragoza P,Manzano R,Osta R

    更新日期:2020-12-16 00:00:00