Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma

Davidson, Ben; Reich, Reuven; Lazarovici, Philip; Flørenes, Viví Ann; Risberg, Bjørn; Nielsen, Søren Laurentius; Sert, Bilal; Bedrossian, Carlos W.M.

doi:10.1016/j.lungcan.2003.11.014

Cited by 61 publications

(69 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, among 41 patients of their study, nearly half of them had adenocarcinoma, thus number of OESCC patients is much lower than our study, which might lead to insufficient evaluation. On the contrary, as our results, most of previous reports regarding other cancers have shown the positive relationship between malignant potential of tumours and expression of NGF or its receptors (Geldof et al, 1998;Schneider et al, 2001;Zhu et al, 2001Zhu et al, , 2002Sakamoto et al, 2001a, b;Kishibe et al, 2002;Davidson et al, 2003;Dolle et al, 2003).…”

Section: Discussioncontrasting

confidence: 51%

“…The expression of TrkA is considered a favourable prognostic factor in several types of cancer (Kramer et al, 1996;Combaret et al, 1997;Descamps et al, 2001a), whereas activation of TrkA by phosphorylation correlates with a poorer clinical outcome in serous ovarian carcinoma (Davidson et al, 2003). Results of the current study revealed that higher expression of NGF is correlated with increased production of phospho-TrkA in OESCC, and suppression of NGF expression resulted in decreased expression of phospho-TrkA in vitro.…”

Section: Discussionmentioning

confidence: 46%

“…A major biological function of NGF is the maintenance and survival of postmitotic neurons, suggesting it may be useful for the treatment of neurodegenerative diseases. In addition to its role in the development and maintenance of neuronal cells, recent studies have shown that NGF and its receptors are found and sometimes even overexpressed outside the nervous system, where it may promote cancer cell proliferation, growth, and invasion in several types of cancer such as breast, pancreas, and prostate cancer (Pflug et al, 1995;Walch and Marchetti, 1999;Sakamoto et al, 2001a, b;Schneider et al, 2001;Zhu et al, 2001Zhu et al, , 2002Kishibe et al, 2002;Davidson et al, 2003;Dolle et al, 2003).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma

et al. 2006

View full text Add to dashboard Cite

Nerve growth factor (NGF) is overexpressed not only in nervous system, but also in several types of cancers. However, the role of NGF in oesophageal squamous cell carcinoma (OESCC) remains unclear. Here, we show the first evidence of NGF-TrkA autocrine loop and clinical significance of NGF overexpression in OESCC. Immunohistochemical study of 109 OESCC specimens revealed that NGF overexpression, found in 63 out of 109 patients (57.8%), was associated with lymph node metastasis, distant metastasis, higher TNM stage, poorer tumour differentiation, and poorer survival. NGF overexpression was also associated with strong expression of TrkA and negative expression of low-affinity neurotrophin receptor (p75NTR). Semiquantitative reverse transcription -polymerase chain reaction (RT -PCR) of 19 surgical specimens showed upregulation of NGF mRNA in 17 out of 19 (89%) patients. All five OESCC cell lines tested in vitro secreted detectable NGF in enzyme-linked immunosorbent assay, and expressed TrkA and p75NTR on RT -PCR and Western blot. The motility of HSA/c, one of the OESCC cell lines overexpressing NGF, was significantly decreased by either neutralising anti-NGF antibody, an inhibitor of TrkA, or NGF-small interfering RNA in transwell migration assay. Our findings suggest that NGF is of potential interest not only as a prognostic factor, but also as a novel therapeutic target in OESCC.

show abstract

Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 46%

mentioning

confidence: 99%

See 1 more Smart Citation

Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Physiologically, the TRK/neurotrophin axis plays a role in neuronal maintenance and survival during development (17). TRK/neurotrophins have, however, also been implicated in cancer: Genetic rearrangement and activation of TRKA, for example, has been found in colon and papillary thyroid cancers (18), and of TRKC in several tumor types (19), whereas autocrine or paracrine activation of TRKs has been implicated in various cancers, including neuroblastoma, mesothelioma, pancreas, prostate, ovarian, and breast carcinomas (20)(21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Dual Targeting of CDK and Tropomyosin Receptor Kinase Families by the Oral Inhibitor PHA-848125, an Agent with Broad-Spectrum Antitumor Efficacy

Albanese

Alzani

Amboldi

et al. 2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Altered expression and activity of cyclin-dependent kinase (CDK) and tropomyosin receptor kinase (TRK) families are observed in a wide variety of tumors. In those malignancies with aberrant CDK activation, the retinoblastoma protein (pRb) pathway is deregulated, leading to uncontrolled cell proliferation. Constitutive activation of TRKs is instead linked to cancer cell survival and dissemination. Here, we show that the novel small-molecule PHA-848125, a potent dual inhibitor of CDKs and TRKs, possesses significant antitumor activity. The compound inhibits cell proliferation of a wide panel of tumoral cell lines with submicromolar IC 50 . PHA-848125-treated cells show cell cycle arrest in G 1 and reduced DNA synthesis, accompanied by inhibition of pRb phosphorylation and modulation of other CDK-dependent markers. The compound additionally inhibits phosphorylation of TRKA and its substrates in cells, which functionally express this receptor. Following oral administration, PHA-848125 has significant antitumor activity in various human xenografts and carcinogen-induced tumors as well as in disseminated primary leukemia models, with plasma concentrations in rodents in the same range as those found active in inhibiting cancer cell proliferation. Mechanism of action was also confirmed in vivo as assessed in tumor biopsies from treated mice. These results show that the dual CDK-TRK inhibitor PHA-848125 has the potential for being a novel and efficacious targeted drug for cancer treatment. Mol Cancer Ther; 9(8); 2243-54. ©2010 AACR.

show abstract

“…Additionally, constitutively active TrkA fusions occur in a subset of papillary thyroid cancers and colon carcinomas (9,18). Autocrine signaling pathway activation involving NGF and TrkA or BDNF and TrkB have been described in subpopulations of mesothelioma and breast and ovarian cancers, and activated Trk expression has been shown to correlate with poor prognosis in these settings (19)(20)(21)(22). Recent data also suggest a role for TrkB and BDNF expression in the survival of multiple myeloma cells (23,24).…”

Section: Introductionmentioning

confidence: 99%

Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway

Thress

Macintyre

Wang

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Tropomyosin-related kinases (TrkA, TrkB, and TrkC) are receptor tyrosine kinases that, along with their ligands, the neurotrophins, are involved in neuronal cell growth, development, and survival. The Trk-neurotrophin pathway may also play a role in tumorigenesis through oncogenic fusions, mutations, and autocrine signaling, prompting the development of novel Trk inhibitors as agents for cancer therapy. This report describes the identification of AZ-23, a novel, potent, and selective Trk kinase inhibitor. In vitro studies with AZ-23 showed improved selectivity over previous compounds and inhibition of Trk kinase activity in cells at low nanomolar concentrations. AZ-23 showed in vivo TrkA kinase inhibition and efficacy in mice following oral administration in a TrkA-driven allograft model and significant tumor growth inhibition in a Trk-expressing xenograft model of neuroblastoma. AZ-23 represents a potent and selective Trk kinase inhibitor from a novel series with the potential for use as a treatment for cancer.

show abstract

Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma

Cited by 61 publications

References 26 publications

Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma

Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma

Dual Targeting of CDK and Tropomyosin Receptor Kinase Families by the Oral Inhibitor PHA-848125, an Agent with Broad-Spectrum Antitumor Efficacy

Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway

Contact Info

Product

Resources

About