Predictive Biomarkers for Molecularly Targeted Therapies in Renal Cell Carcinoma

Brugarolas, James

doi:10.6004/jnccn.2016.0095

Cited by 4 publications

(4 citation statements)

References 18 publications

(24 reference statements)

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“…Inactivation of PTEN causes elevated AKT activation. The most important gene mutations for the development and progression of metastatic disease are: PIK3CA -playing a role in tumor cell invasion, and KRAS -an oncogene involved in signal transduction in hypoxia-inducible pathway activated by epidermal growth factor receptor (EGFR), which become targets for drug intervention in RCC [1,6,9].…”

Section: Introductionmentioning

confidence: 99%

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Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Gasińska

Jaszczyński

Adamczyk

et al. 2019

Folia Histochem Cytobiol.

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Introduction. It has been suggested that the metastatic potential of neoplastic cells can be predicted on the basis of their biological features, including expression of proteins involved in the epithelial to mesenchymal transition (EMT). Therefore, the purpose of this work was to (1) evaluate the expression of EMT markers: ZEB2, vimentin, N-cadherin, TWIST, PTEN, survivin, E-cadherin, Ki-67 and GLUT-1, (2) assess mutation status of two genes: PIK3CA and KRAS, and (3) investigate the potential relationships between the studied biomarkers and clinicopathological factors in clear-cell renal cell carcinoma (ccRCC). Material and methods. Tumor tissue samples (embedded in paraffin blocks) from 159 patients undergoing radical nephrectomy were analyzed. Proteins expression was evaluated immunohistochemically. DNA mutations were analyzed on DNA isolated from tumor tissue and amplified by real-time PCR detection using suitable fluorescent labeled TaqMan assays. Results. One hundred and seven men and 52 women of mean age of 63.1years were enrolled. Fifty four cancers at pTNM stage I-II and 98 at pTNM III-IV stage were diagnosed. There were 30 Fuhrman grade G1, 61 Fuhrman G2, 49 Fuhrman G3 and 19 Fuhrman G4 tumors. A negative correlation between ZEB2 (p = 0.047, r = -0.172) or E-cadherin expression (p = 0.027, r = -0.191) and TNM was observed. Positive association between grade and Ki-67 (p < 0.001), survivin (p < 0.001), vimentin (p < 0.001) immunoreactivity and negative association between TWIST expression (p = 0.029) or PTEN expression (p = 0.013) were found. Ki-67 expression was positively correlated with survivin (p < 0.001, r = 0.617), vimentin (p = 0.001, r = 0.251) and N-cadherin (p = 0,009, r = 0.207) immunoreactivity which can suggest tumor aggressiveness. TWIST was negatively correlated with E-cadherin (p < 0.001, r = -0.284), vimentin (p < 0.001, r = -0.297) and N-cadherin (p < 0.002, r = -0.241). ZEB2 was not associated with ccRCC grade but was negatively correlated with E-cadherin (p = 0.055, r= -0.153) and PTEN (p = 0.006). GLUT-1 expression was inversely linked to E-cadherin expression (p = 0.022, r= -0.182). Mutations in PIK3CA and KRAS genes were not found in any of the studied ccRCC tumors. Conclusions. Low-grade tumors showed higher expression of ZEB2 and TWIST proteins than high-grade tumors, which can suggest that EMT in ccRCC begins at early stages of tumor development and, therefore, evaluation of these proteins, together with other biomarkers, may be useful for assessment of the tumor metastatic potential.

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Section: Introductionmentioning

confidence: 99%

“…Epithelial-mesenchymal transition (EMT) is related to proliferation, invasion and metastasis of tumor [5,9,10]. Increased cell proliferation can be detected by the assessment of expression of the Ki-67 antigen, which is present during all active phases of the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Gasińska

Jaszczyński

Adamczyk

et al. 2019

Folia Histochem Cytobiol.

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show abstract

“…Izolowane lub skojarzone leczenie wymienionymi cytokinami znajduje powszechne zastosowanie jako terapia pierwszego rzutu u chorych z RCC we wczesnym stadium rozwoju. Mimo niezadowalających wyników w leczeniu zaawansowanego raka nerki [9], do 2005 roku immunoterapia oparta na podawaniu wysokiej dawki IL-2 stanowiła jedyny schemat leczenia wykazujący jakiekolwiek efekty kliniczne [17]. Późniejszy rozwój terapii celowanych doprowadził do zmiany strategii terapeutycznych u chorych w zaawansowanym stadium jasnokomórkowego raka nerki.…”

Section: Dyskusjaunclassified

“…Poznanie centralnej roli szlaku sygnałowego PI3K/Akt/mTOR w patogenezie nowotworzenia doprowadziło do opracowania leków specyficznie celujących w poszczególne etapy aktywacji szlaku PI3K/Akt/mTOR [7,17]. W przedstawionych badaniach podjęto próbę oceny potencjału terapeutycznego i wykluczenia immunosupresyjnego wpływu Temsirolimusu u myszy cierpiących na RCC.…”

Section: Wiktoria Maria Suchorska Mikołaj Nowak / Zeszyty Naukowe Wcunclassified

Ocena potencjału terapeutycznego Temsirolimusu w zaawansowanym stadium renal cell carcinoma

Suchorska

Nowak²

2017

los

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Assessment of Early Tumour Shrinkage: Ready for Integration in the Treatment Strategy for Metastatic Renal Cell Carcinoma?

Albigès

Escudier

2016

European Urology

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Predictive Biomarkers for Molecularly Targeted Therapies in Renal Cell Carcinoma

Cited by 4 publications

References 18 publications

Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Ocena potencjału terapeutycznego Temsirolimusu w zaawansowanym stadium renal cell carcinoma

Assessment of Early Tumour Shrinkage: Ready for Integration in the Treatment Strategy for Metastatic Renal Cell Carcinoma?

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