Resistance to tyrosine kinase inhibitors in clear cell renal cell carcinoma: From the patient's bed to molecular mechanisms

Buczek, Magdalena Elżbieta; Escudier, Bernard; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

doi:10.1016/j.bbcan.2013.10.001

Cited by 75 publications

(76 citation statements)

References 110 publications

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“…Although radiotherapy technology is continuously improving, the treatment effect of patients with carcinoma who receive radiotherapy is unsatisfactory, mainly due to radioresistance (1). Our previous study indicated that a significant negative correlation was present between the length of the telomeres and radiosensitivity in the same tissue-derived cell lines (2).…”

Section: Introductionmentioning

confidence: 99%

Expression of human protection of telomere 1 correlates with telomere length and radiosensitivity in the human laryngeal cancer Hep-2 cell line

et al. 2015

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Abstract. The close association between telomere length and radiosensitivity has been established by several studies. There is also a hypothesis that telomere length may be regulated by human protection of telomere 1 (hPOT1) in human carcinoma cells. In the present study, the hPOT1 level between the radioresistant Hep-2R cells and the wild-type were compared, and the results showed that the hPOT1 gene was upregulated in the radioresistant Hep-2R cell lines compared with the wild-type. This suggested that the expression level of hPOT1 correlates with radiosensitivity. Additionally, an hPOT1-directed short hairpin (sh)RNA plasmid was constructed and transferred into the Hep-2R cells, which lead to telomere shortening, an increase in apoptosis and markedly decreased growth of the RNAi-Hep-2R cell line. These results demonstrate that hPOT1-directed shRNAs are associated with telomere length and radiosensitivity, and maybe a potent sensitizer for laryngeal cancer radiotherapy.

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Section: Introductionmentioning

confidence: 99%

Expression of human protection of telomere 1 correlates with telomere length and radiosensitivity in the human laryngeal cancer Hep-2 cell line

et al. 2015

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“…Mutations of VHL result in constitutive stabilization of the HIF-1α subunit, leading to highly angiogenic malignancy (9). This phenomenon occurs due to overexpression of vascular endothelial growth factor (VEGF), its receptors (VEGFR1, VEGFR2 and VEGFR3), and platelet-derived growth factor (PDGF) receptors in response to constitutive activation of HIF-1α (10,11).…”

Section: Introductionmentioning

confidence: 99%

Hormone signaling pathways as treatment targets in renal cell cancer (Review)

Czarnecka

Niedzwiedzka

Porta

et al. 2016

International Journal of Oncology

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Abstract. Epidemiological, clinical, biochemical and genetic research has revealed that renal cell cancer (RCC) etiology is hormone-related. It was shown that hormone receptors are abnormally expressed in RCC cells. Abnormal endocrine stimulation also plays a significant role in RCC pathophysiology. Cellular proliferation, migration, angiogenesis, and drug resistance in RCC is modulated by para-and autocrine hormonal stimulation. In particular, RCC overexpression of gonadotropin-releasing hormone and its receptor was reported. On the contrary, corticotropin releasing hormone was reported to inhibit RCC cell proliferation and regulate angiogenesis. Overexpression of luteinizing hormone also promotes RCC tumor angiogenesis. Estrogen receptor α overexpression increases the transcriptional factor activity of hypoxia inducible factor HIF-1α, but estrogen receptor β has a cancer suppressive role. Glucocorticoid receptors and androgen receptor are markers of indolent RCC and assigned tumor suppressive activity. Proopiomelanocortin is upregulated in VHL-mutated renal cell carcinoma via Nur77 transcription factor signaling. In RCC, follicle-stimulating hormone receptor promotes angiogenesis and metastatic formation via VEGF release. Mineralocorticoid receptor overexpression promotes cell survival and increases RCC cell proliferation. Vitamin D receptor expression is downregulated or absent in RCC and differentiate subtypes of renal cell tumors. RAR-β promotes tumorigenesis but retinoic acid receptor γ expression correlates negatively with the TNM stage at diagnosis. Finally, progesterone receptor expression is negatively correlated with the cancer stage. Molecular data analysis revealed the possibility of renal cancer cell proliferation induction via hormone activated pathways. Inhibition of hormonal signaling may thus play a putative role in supportive therapies against this cancer type.

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“…However, the development of resistance to antiangiogenic therapies is nearly universal. Upon developing resistance to VEGFTKIs, many tumors produce very high levels of VEGF [ 120 ]. Given the high levels of VEGF in most RCC and as well as the immune-modulatory effects of VEGF, combinations with VEGF-TKIs (and nivolumab) or the monoclonal anti-VEGF antibody bevacizumab (and MPDL3280A) are currently underway and have been reasonably well tolerated in early phase trials [ 121 , 122 ].…”

Section: Pd-1 Plus Antiangiogenicmentioning

confidence: 99%