Translational research in neuroendocrine tumors: pitfalls and opportunities.

Abstract:

:Interest in research on neuroendocrine tumors (NETs) has grown in the past 10 years, coinciding with improvements in our understanding of the molecular pathogenesis of NETs. In addition, NETs have become one of the most exciting settings for drug development. Two targeted agents for the management of advanced pancreatic NETs have been approved, but the development of targeted agents for NETs is limited by problems with both patient selection and demonstration of activity. In this review, we analyze these limitations and discuss ways to increase the predictive value of preclinical models for target discovery and drug development. The role of translational research and 'omics' methodologies is emphasized, with the final aim of developing personalized medicine. Because NETs usually grow slowly and metastatic tumors are found at easily accessible locations, and owing to improvements in techniques for liquid biopsies, NETs provide a unique opportunity to obtain tumor samples at all stages of the evolution of the disease and to adapt treatment to changes in tumor biology. Combining clinical and translational research is essential to achieve progress in the NET field. Slow growth and genetic stability limit and challenge both the availability and further development of preclinical models of NETs, one of the most crucial unmet research needs in the field. Finally, we suggest some useful approaches for improving clinical drug development for NETs: moving from classical RECIST-based response end points to survival parameters; searching for different criteria to define response rates (for example, antiangiogenic effects and metabolic responses); implementing randomized phase II studies to avoid single-arm phase II studies that produce limited data on drug efficacy; and using predictive biomarkers for patient selection.

journal_name

Oncogene

journal_title

Oncogene

authors

Capdevila J,Casanovas O,Salazar R,Castellano D,Segura A,Fuster P,Aller J,García-Carbonero R,Jimenez-Fonseca P,Grande E,Castaño JP

doi

10.1038/onc.2016.316

subject

Has Abstract

pub_date

2017-04-06 00:00:00

pages

1899-1907

issue

14

eissn

0950-9232

issn

1476-5594

pii

onc2016316

journal_volume

36

pub_type

杂志文章,评审

相关文献

ONCOGENE文献大全
  • Bcl-2 and calcium: controversy beneath the surface.

    abstract::The function of Bcl-2 family members on the endoplasmic reticulum has received increasing attention in recent years. The endoplasmic reticulum is the major organelle involved in intracellular calcium homeostasis and calcium signaling, including calcium signals that mediate apoptosis induction by anticancer drugs. But ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1207519

    authors: Distelhorst CW,Shore GC

    更新日期:2004-04-12 00:00:00

  • Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells.

    abstract::Pancreatic cancer still remains one of the most lethal diseases and establishment of new therapy is needed. The purpose of this study is to find novel factors involved in pancreatic cancer progression by proteomic approach. We compared pre- and postoperative serum protein profiling obtained from pancreatic cancer pati...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210951

    authors: Takano S,Yoshitomi H,Togawa A,Sogawa K,Shida T,Kimura F,Shimizu H,Tomonaga T,Nomura F,Miyazaki M

    更新日期:2008-05-01 00:00:00

  • Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization.

    abstract::Glioblastoma (GBM) is a highly malignant glioma, which has the propensity to infiltrate throughout the brain in contrast to pilocytic astrocytoma (PA) of the posterior fossa, which does not spread and can be cured by surgery. We have used Suppression Subtractive Hybridization to define markers that better delineate th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209305

    authors: Colin C,Baeza N,Bartoli C,Fina F,Eudes N,Nanni I,Martin PM,Ouafik L,Figarella-Branger D

    更新日期:2006-05-04 00:00:00

  • Drosophila actin-Capping Protein limits JNK activation by the Src proto-oncogene.

    abstract::The Src family kinases c-Src, and its downstream effectors, the Rho family of small GTPases RhoA and Jun N-terminal kinase (JNK) have a significant role in tumorigenesis. In this report, using the Drosophila wing disc epithelium as a model system, we demonstrate that the actin-Capping Protein (CP) αβ heterodimer, whic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.155

    authors: Fernández BG,Jezowska B,Janody F

    更新日期:2014-04-17 00:00:00

  • NF-kappaB signaling, liver disease and hepatoprotective agents.

    abstract::The NF-kappaB signaling pathway has particular relevance to several liver diseases including hepatitis (liver infection by Helicobacter, viral hepatitis induced by HBV and HCV), liver fibrosis and cirrhosis and hepatocellular carcinoma. Furthermore, the NF-kappaB signaling pathway is a potential target for development...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2008.300

    authors: Sun B,Karin M

    更新日期:2008-10-20 00:00:00

  • Isolation of chromosome-specific DNA sequences from an Alu polymerase chain reaction library to define the breakpoint in a patient with a constitutional translocation t(1;13) (q22;q12) and ganglioneuroblastoma.

    abstract::We describe the cytogenetic and molecular characterization of a t(1;13)(q22;q12) constitutional rearrangement occurring in a patient with a relatively benign form of neuroblastoma, called ganglioneuroblastoma. Somatic cell hybrids were generated between mouse 3T3 cells and a lymphoblastoid cell line from this patient,...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Michalski AJ,Cotter FE,Cowell JK

    更新日期:1992-08-01 00:00:00

  • Aggrus: a diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors.

    abstract::Aggrus (also known as T1alpha/podoplanin) is a membrane sialoglycoprotein whose function in tumors is unknown. We recently determined that Aggrus possessed the ability of inducing platelet aggregation and that its expression was frequently upregulated in colorectal tumors. Thus, Aggrus expression might be associated w...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207869

    authors: Kato Y,Sasagawa I,Kaneko M,Osawa M,Fujita N,Tsuruo T

    更新日期:2004-11-04 00:00:00

  • Induction of a caffeine-sensitive S-phase cell cycle checkpoint by psoralen plus ultraviolet A radiation.

    abstract::Induction of interstrand crosslinks (ICLs) in chromosomal DNA is considered a major reason for the antiproliferative effect of psoralen plus ultraviolet A (PUVA). It is unclear as to whether PUVA-induced cell cycle arrest is caused by ICLs mechanically stalling replication forks or by triggering cell cycle checkpoints...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206613

    authors: Joerges C,Kuntze I,Herzinger T

    更新日期:2003-09-18 00:00:00

  • UDP-glucose 6-dehydrogenase regulates hyaluronic acid production and promotes breast cancer progression.

    abstract::An improved understanding of the biochemical alterations that accompany tumor progression and metastasis is necessary to inform the next generation of diagnostic tools and targeted therapies. Metabolic reprogramming is known to occur during the epithelial-mesenchymal transition (EMT), a process that promotes metastasi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0885-4

    authors: Arnold JM,Gu F,Ambati CR,Rasaily U,Ramirez-Pena E,Joseph R,Manikkam M,San Martin R,Charles C,Pan Y,Chatterjee SS,Den Hollander P,Zhang W,Nagi C,Sikora AG,Rowley D,Putluri N,Zhang XH,Karanam B,Mani SA,Sreekumar A

    更新日期:2020-04-01 00:00:00

  • Isolation of a distinct class of gain-of-function SHP-2 mutants with oncogenic RAS-like transforming activity from solid tumors.

    abstract::SHP-2 protein tyrosine phosphatase plays an important role in activation of the RAS-dependent signaling. Gain-of-function mutations in the PTPN11 gene, which encodes SHP-2, have been found in the leukemia-prone developmental disorder Noonan syndrome as well as sporadic childhood leukemias, indicating that SHP-2 is a b...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1211019

    authors: Miyamoto D,Miyamoto M,Takahashi A,Yomogita Y,Higashi H,Kondo S,Hatakeyama M

    更新日期:2008-06-05 00:00:00

  • Constitutive activation of the shh-ptc1 pathway by a patched1 mutation identified in BCC.

    abstract::Mutations in the transmembrane receptor patched1 (ptc1) are responsible for the majority of basal cell carcinoma (BCC) cases. Many of these mutations, including ptc1-Q688X, result in premature truncation of the ptc1 protein. ptc1-Q688X has been identified in patients with both BCC and nevoid basal cell carcinoma syndr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208240

    authors: Barnes EA,Heidtman KJ,Donoghue DJ

    更新日期:2005-01-27 00:00:00

  • TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA.

    abstract::The cancer-prone and premature aging disease Werner syndrome is due to loss of WRN gene function. Cells lacking WRN demonstrate genomic instability, including telomeric abnormalities and undergo premature senescence, suggesting defects in telomere metabolism. This notion is strongly supported by our finding of physica...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206906

    authors: Machwe A,Xiao L,Orren DK

    更新日期:2004-01-08 00:00:00

  • The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer.

    abstract::Beta-transducin repeats-containing proteins (beta-TrCP) serve as the substrate recognition subunits for the SCFbeta-TrCP E3 ubiquitin ligases. These ligases ubiquitinate specifically phosphorylated substrates and play a pivotal role in the regulation of cell division and various signal transduction pathways, which, in...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1207389

    authors: Fuchs SY,Spiegelman VS,Kumar KG

    更新日期:2004-03-15 00:00:00

  • CFP suppresses breast cancer cell growth by TES-mediated upregulation of the transcription factor DDIT3.

    abstract::Breast cancer is a heterogeneous genetic disease driven by the accumulation of individual mutations per tumor. Whole-genome sequencing approaches have identified numerous genes with recurrent mutations in primary tumors. Although mutations in well characterized tumor suppressors and oncogenes are overrepresented in th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0739-0

    authors: Block I,Müller C,Sdogati D,Pedersen H,List M,Jaskot AM,Syse SD,Lund Hansen P,Schmidt S,Christiansen H,Casella C,Bering Olsen S,Blomstrøm MM,Riedel A,Thomassen M,Kruse TA,Karlskov Hansen SW,Kioschis P,Mollenhauer J

    更新日期:2019-06-01 00:00:00

  • Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2.

    abstract::The c-erbB-2 proto-oncogene encodes a receptor tyrosine kinase (RTK) closely related to the epidermal growth factor receptor (EGFR). Overexpression of erbB-2 occurs in approximately 20% of human breast tumours, where increased expression correlates with poor patient prognosis. The EGFR is coupled to the Ras signalling...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Janes PW,Daly RJ,deFazio A,Sutherland RL

    更新日期:1994-12-01 00:00:00

  • TRPS1 regulates oestrogen receptor binding and histone acetylation at enhancers.

    abstract::The chromatin state is finely tuned to regulate function and specificity for transcription factors such as oestrogen receptor alpha (ER), which contributes to cell growth in breast cancer. ER transcriptional potential is mediated, in large part, by the specific associated proteins and co-factors that interact with it....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0312-2

    authors: Serandour AA,Mohammed H,Miremadi A,Mulder KW,Carroll JS

    更新日期:2018-09-01 00:00:00

  • Cholecystokinin-2 receptor modulates cell adhesion through beta 1-integrin in human pancreatic cancer cells.

    abstract::Several lines of evidence suggest that gastrin and the CCK-2 receptor (CCK2R) could contribute to pancreatic carcinogenesis by modulating processes such as proliferation, cell adhesion or migration. In the current study, we used a 'cancer gene array' and identified beta1-integrin subunit as a new gastrin-regulated gen...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209484

    authors: Cayrol C,Clerc P,Bertrand C,Gigoux V,Portolan G,Fourmy D,Dufresne M,Seva C

    更新日期:2006-07-27 00:00:00

  • HSP110 promotes colorectal cancer growth through STAT3 activation.

    abstract::Heat shock protein 110 (HSP110) is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps cells survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently shown that colorectal cancer patients with microsatellite instability (MSI) had an...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.403

    authors: Berthenet K,Bokhari A,Lagrange A,Marcion G,Boudesco C,Causse S,De Thonel A,Svrcek M,Goloudina AR,Dumont S,Hammann A,Biard DS,Demidov ON,Seigneuric R,Duval A,Collura A,Jego G,Garrido C

    更新日期:2017-04-20 00:00:00

  • An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells.

    abstract::Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formati...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.512

    authors: Zhang HR,Wang XD,Yang X,Chen D,Hao J,Cao R,Wu XZ

    更新日期:2017-07-06 00:00:00

  • Transfection of K-rasAsp12 cDNA markedly elevates IL-1beta- and lipopolysaccharide-mediated inducible nitric oxide synthase expression in rat intestinal epithelial cells.

    abstract::Activating mutations of K-ras are frequent in colon tumors and aberrant crypt foci, and may play important roles in colon carcinogenesis. Here, we investigated the effects of a K-ras codon 12 mutation on inducible nitric oxide synthase (iNOS) expression. When rat intestinal epithelial cells (IEC-6) were transfected wi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207051

    authors: Takahashi M,Mutoh M,Shoji Y,Kamanaka Y,Naka M,Maruyama T,Sugimura T,Wakabayashi K

    更新日期:2003-10-23 00:00:00

  • CHF: a novel factor binding to cyclin A CHR corepressor element.

    abstract::Cell cycle modulation of cyclin A expression is due to the periodic relief of a transcriptional repression mediated by a bipartite negative DNA regulatory region. The 5' element (Cell Cycle Responsive Element: CCRE; cell Cycle Dependent Element: CDE) is clearly occupied in a cyclic manner in vivo, whereas the 3' eleme...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203017

    authors: Philips A,Chambeyron S,Lamb N,Vié A,Blanchard JM

    更新日期:1999-11-04 00:00:00

  • Direct association of YY-1 with c-Myc and the E-box binding protein in regulation of glycophorin gene expression.

    abstract::We previously reported that YY-1, a versatile transcription factor, regulates expression of glycophorin gene by binding to its locus control region-like region (Gp-LCR) in combination with E-box binding protein during murine erythroleukemia (MEL) cell differentiation. In the present work, we demonstrated that YY-1 and...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202026

    authors: Zhao JH,Inoue T,Shoji W,Nemoto Y,Obinata M

    更新日期:1998-08-27 00:00:00

  • Hepatitis B virus X protein promotes the development of liver fibrosis and hepatoma through downregulation of miR-30e targeting P4HA2 mRNA.

    abstract::Hepatitis B virus (HBV)-induced liver necrosis takes great part in liver cirrhosis progression. However, less is known about whether hepatitis B virus X protein (HBx) has effect on liver fibrosis. Here, we report that HBV leads to liver fibrosis and hepatocarcinogenesis through miR-30e targeting P4HA2. HBV transgenic ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.291

    authors: Feng GX,Li J,Yang Z,Zhang SQ,Liu YX,Zhang WY,Ye LH,Zhang XD

    更新日期:2017-12-14 00:00:00

  • Mutations of tumor necrosis factor alpha-responsive serine residues within the C-terminal transactivation domain of human transcription factor REL enhance its in vitro transforming ability.

    abstract::The human c-rel gene (REL), encoding an NF-kappaB transcription factor, is amplified or mutated in several human B-cell lymphomas and can transform chicken lymphoid cells in vitro. We have previously shown that certain deletions of C-terminal transactivation sequences enhance REL's transforming ability in chicken sple...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208902

    authors: Starczynowski DT,Reynolds JG,Gilmore TD

    更新日期:2005-11-10 00:00:00

  • Type I collagen is a molecular target for inhibition of angiogenesis by endogenous thrombospondin-1.

    abstract::Three-dimensional explant cultures of muscle tissue were used to characterize secreted proteins regulated by endogenous levels of the angiogenesis modulator thrombospondin (TSP)-1. Explants from TSP1 null mice exhibit enhanced neovascularization associated with increased endothelial outgrowth but decreased outgrowth o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209069

    authors: Zhou L,Isenberg JS,Cao Z,Roberts DD

    更新日期:2006-01-26 00:00:00

  • The domain of p53 required for binding HPV 16 E6 is separable from the degradation domain.

    abstract::The E6 proteins of specific cancer-associated human papillomaviruses (HPVs) complex with and mediate degradation of the cellular anti-oncogene p53 in vitro. A critical property of p53 is its ability to stimulate transcription from promoters containing its recognition sequence. HPV E6, mutant p53 proteins, and several ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Mansur CP,Marcus B,Dalal S,Androphy EJ

    更新日期:1995-02-02 00:00:00

  • CBL enhances breast tumor formation by inhibiting tumor suppressive activity of TGF-β signaling.

    abstract::Casitas B-lineage lymphoma (CBL) protein family functions as multifunctional adaptor proteins and E3 ubiquitin ligases that are implicated as regulators of signaling in various cell types. Recent discovery revealed mutations of proto-oncogenic CBL in the linker region and RING finger domain in human acute myeloid neop...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.18

    authors: Kang JM,Park S,Kim SJ,Hong HY,Jeong J,Kim HS,Kim SJ

    更新日期:2012-12-13 00:00:00

  • Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation.

    abstract::Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated ApcΔ716 Trp53LSL•R270H villin-Cr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.194

    authors: Nakayama M,Sakai E,Echizen K,Yamada Y,Oshima H,Han TS,Ohki R,Fujii S,Ochiai A,Robine S,Voon DC,Tanaka T,Taketo MM,Oshima M

    更新日期:2017-10-19 00:00:00

  • Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2.

    abstract::Branching morphogenesis within the peripubertal mouse mammary gland is directed by progesterone (P). A role for the homeobox-containing transcription factor, Msx2, during branching morphogenesis is suggested from its ontogenic expression profile and hormonal regulation. Herein, we define the spatio-temporal control of...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210555

    authors: Satoh K,Hovey RC,Malewski T,Warri A,Goldhar AS,Ginsburg E,Saito K,Lydon JP,Vonderhaar BK

    更新日期:2007-11-29 00:00:00

  • Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR.

    abstract::Epigenetic regulation of gene expression is critical in the maintenance of cellular homeostasis. Dysregulation of normal epigenetic transcription occurs in abnormal physiological conditions, such as those seen in cancer cells and cells infected with parasites, making the mechanism underlying abnormal epigenetic transc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208394

    authors: Ego T,Tanaka Y,Shimotohno K

    更新日期:2005-03-10 00:00:00