The insulin-like growth factor pathway as a target for cancer therapy

Lopez-Calderero, Iker; Chavez, Elizabeth S.; García‐Carbonero, Rocío

doi:10.1007/s12094-010-0514-8

Cited by 23 publications

(11 citation statements)

References 78 publications

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“…The IGF signaling pathway plays a key role in malignant transformation and cancer progression and is also of interest as a target for cancer therapy (see e.g. [13]). Plasma levels of IGF binding protein 2 (IGFBP2), which in its phosphorylated form can regulate localization and translation of IGF2 mRNA [14], has been evaluated as a diagnostic marker in adrenocortical tumors, but it was not considered sensitive enough to be used clinically [15].…”

Section: Resultsmentioning

confidence: 99%

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

et al. 2014

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We have compared the microsomal protein composition of eight malignant and six benign adrenocortical tumors with proteomic methods. IGF2 had increased level in the malignant tumors, confirming previous microarray studies on the same material. Aldolase A, a glycolytic enzyme, also showed increased levels in the malignant tissue compared to the benign. Additionally, several proteins belonging to complex I in the mitochondrial respiration chain showed decreased levels in the malignant tissue. Taken together, this may indicate a shift in energy metabolism where glycolysis may be favored over tight coupling of glycolysis and mitochondrial respiration, a phenomenon known as the Warburg effect. One of the complex I proteins that showed decreased levels in the malignant tissue was GRIM-19. This protein has been suggested as a tumor suppressive protein by being a negative regulator of STAT3. In summary, an analysis of the microsomal proteome in adrenocortical tumors identifies groups of proteins as well as specific proteins differentially expressed in the benign and malignant forms. These proteins shed light on the biology behind malignancy and could delineate future drug targets.

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Section: Resultsmentioning

confidence: 99%

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

et al. 2014

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“…In addition, IGF‐1‐induced proliferation of quiescent metastatic uveal melanoma cell line was strongly inhibited by anti‐IGF‐1R antibody while only slight inhibition (data not shown) was observed in FBS‐stimulated quiescent cells. In fact, results of cancer clinical trials using anti‐IGF‐1R antibody have been disappointing (Lopez‐Calderero et al., ). One of the reasons for the lack of efficacy might be explained by alternative mechanisms of cell growth through other growth factor receptors (Haluska et al., ).…”

Section: Discussionmentioning

confidence: 99%

Expression of insulin‐like growth factor‐1 receptor in metastatic uveal melanoma and implications for potential autocrine and paracrine tumor cell growth

Yoshida

Selvan

McCue

et al. 2014

Pigment Cell Melanoma Res

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We investigated the importance of the insulin-like growth factor-1 receptor (IGF-1R) in hepatic metastases of uveal melanoma. The expression pattern of IGF-1R in archival tissue samples of hepatic metastasis from 24 patients was analyzed by immunohistochemistry. All the samples of hepatic metastases stained positive for IGF-1R. To investigate the biological role of IGF-1R on the growth of metastatic uveal melanoma, a long-term cell line obtained from a hepatic metastasis (TJU-UM001) was evaluated. TJU-UM001 expressed cell surface IGF-1R (>90%) and proliferated in response to exogenous and endogenous insulin-like growth factor-1 (IGF-1). Correlatively, anti-IGF-1R antibody completely blocked IGF-1-induced growth of TJU-UM001 cells. IGF-1 preferentially induced phosphorylation of Akt (S473) in quiescent TJU-UM001 cells, and this was blocked by anti-IGF-1R antibody. This study suggests that autocrine and paracrine mechanisms underlie IGF-1-induced growth of metastatic uveal melanoma and underscore the potential benefit of IGF-1 or IGF-1R antagonism in treatment for metastatic uveal melanoma.

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“…Interestingly, EGFR and IGF‐1R share common properties, and in some tumors including grade IV glioblastoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, IGF‐1R has been identified as a potential source of resistance to EGFR therapies,21‐24 suggesting that dual blockage may provide greater therapeutic effects 25‐27. Consequently, multiple phase 1‐2 clinical trials testing IGF‐1R inhibitors in a diverse number of epithelial cancers, including pancreatic ductal adenocarcinoma, are currently ongoing 28‐36…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma

Valsecchi

McDonald

Brody

et al. 2011

Cancer

104

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BACKGROUND: The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and insulinlike growth factor 1 receptor (IGF‐1R) proteins and IGF‐1R gene copy numbers in pancreatic ductal adenocarcinoma in relation to patients' characteristics and prognosis. METHODS: Immunohistochemical staining was performed on formalin‐fixed paraffin‐embedded tissue derived from tumor specimens recovered during surgery. Slides were evaluated for membranous EGFR and IGF‐1R staining using both the HercepTest and the semiquantitative H‐score systems. Chromogenic in situ hybridization was performed to quantify IGF‐1R gene copy number. The primary outcome was the association between EGFR expression, IGF‐1R expression—in both neoplastic epithelial and stromal cells—or IGF‐1R gene copy number and overall survival. Secondary outcomes included associations between EFGR and IGF‐1R expression and pathologic variables. RESULTS: A total of 105 patients were included. EGFR expression was present in 30.4% of cases and was associated with lymph node metastasis (P = .038). IGF‐1R was overexpressed in 53% of tumors and correlated with higher tumor grade (P = .033). High membranous expression of EGFR (P < .001) and/or IGF‐1R (P = .004), the cytoplasmic detection of EGFR (P = .027), and high expression levels of IGF‐1R in the tumoral stroma (P < .001) were all associated with shorter overall survival, being significantly better in patients who simultaneously do not express membranous EGFR or stromal IGF‐1R. CONCLUSIONS: EGFR and IGF‐1R expression, in neoplastic and stromal cells, seems to be an important prognostic factor. Cancer 2012;3484–3493. © 2011 American Cancer Society.

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The insulin-like growth factor pathway as a target for cancer therapy

Cited by 23 publications

References 78 publications

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

Expression of insulin‐like growth factor‐1 receptor in metastatic uveal melanoma and implications for potential autocrine and paracrine tumor cell growth

Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma

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