Management of metastatic renal cell carcinoma: current trends

Mohammed, Aza; Shergill, Iqbal; Little, Barbara J.

doi:10.1586/14737159.9.1.75

Cited by 16 publications

(15 citation statements)

References 55 publications

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“…Notably, the global incidence of RCC has increased over the past two decades at a rate of 2% per year [2]. Furthermore, RCC is generally resistant to chemotherapy and radiation therapy [3,4]. Therefore, it is essential to discover new therapeutic strategies for treating RCC.…”

Section: Introductionmentioning

confidence: 99%

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Guo

Gui

2018

Cell Physiol Biochem

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Background/Aims: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. Methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression was achieved by RNA interference, which was confirmed by qRT-PCR and Western blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a flow cytometry analysis, respectively. Cell migration and invasion were determined by the scratch and transwell assays. Following the knockdown of ACSS2 expression, the expression of the autophagy-related factor LAMP1 was measured by qRT-PCR and Western blotting. Results: Compared to adjacent tissues, ACSS2 expression was upregulated in RCC cancer tissues and positively correlated with metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell migration and invasion. ACSS2 was determined to promote the expression of LAMP1, which can also promote cell migration. This pathway may be considered a potential mechanism through which ACSS2 participates in RCC development. Conclusion: These data suggest that ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. Taken together, these findings reveal a potential target for the diagnosis and treatment of RCC.

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Section: Introductionmentioning

confidence: 99%

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Guo

Gui

2018

Cell Physiol Biochem

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“…The main histological subtypes are clear cell (75%), papillary (15%) and chromophobe RCC (5%) (Sandim et al 2010). Unfortunately, around 40% of the patients have locally advanced or metastatic disease at the time of diagnosis (Mohammed et al 2009). Due to a lack of sensitivity to chemotherapy and radiotherapy, the prognosis of patients with metastatic RCC is poor with a 5-year survival rate lower than 10% (Ather et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma

Lei

Zhong

Sun

et al. 2011

J Cancer Res Clin Oncol

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“…1 Approximately 85% of RCC tumors have clear-cell histology, characterized by over-expression of VEGF and PDGF. 2, 3 As VEGF and PDGF tyrosine kinases mediate tumor progression via multiple mechanisms, their simultaneous inhibition by linifanib may result in greater antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure

Tannir

Wong

Kollmannsberger

et al. 2011

European Journal of Cancer

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Purpose This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib. Materials and Methods This open-label, multicenter, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary endpoint was objective response rate (ORR) per RECIST by central imaging. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and time to progression (TTP). Safety was also assessed. Results Fifty-three patients, median age 61 years (range 40–80) were enrolled (August 2007 to October 2008) across 12 North-American centers. Median number of prior therapies was two (range 1–4); 42 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4 months (95% CI: 3.6, 6.0) and TTP was the same; median OS was 14.5 months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhea (74%), fatigue (74%), and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%). Conclusions Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25 mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials.

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Management of metastatic renal cell carcinoma: current trends

Cited by 16 publications

References 55 publications

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma

Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure

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