The current status of immunobased therapies for metastatic renal-cell carcinoma

Sathianathen, Niranjan; Krishna, Suprita; Anderson, John; Weight, Christopher J.; Gupta, Shilpa; Konety, Badrinath R.; Griffith, Thomas S.

doi:10.2147/itt.s134850

Cited by 15 publications

(11 citation statements)

References 91 publications

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“…1 Immunotherapy has been a viable treatment since the 1990s, but the advent of immune checkpoint inhibition has improved therapy responses considerably. 2,3 Predictive biomarkers for rational patient selection are currently under extensive investigation. 4 Recently, the apelin receptor (coded by the APLNR gene) was identified as prerequisite for successful cancer immunotherapy, with APLNR deficiency associated with immunotherapy failure.…”

Section: Introductionmentioning

confidence: 99%

Apelin and apelin receptor expression in renal cell carcinoma

et al. 2019

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BACKGROUND: The APLNR (apelin receptor) has been shown to be an essential gene for cancer immunotherapy, with deficiency in APLNR leading to immunotherapy failure. The aim of this study is to investigate the expression of APLN (apelin) and APLNR in patients with renal cell carcinoma (RCC), and its association with clinicopathological parameters and survival. METHODS: Three well-characterised patient cohorts with RCC were used: Study cohort 1 (clear-cell RCC; APLN/APLNR mRNA expression; n = 166); TCGA validation cohort (clear-cell RCC; APLN/APLNR mRNA expression; n = 481); Study cohort 2 (all RCC subtypes; APLNR protein expression/immunohistochemistry; n = 300). Associations between mRNA/protein expression and clinicopathological variables/patients' survival were tested statistically. RESULTS: While APLN showed only very weak association with tumour histological grade (TCGA cohort), APLNR/mRNA protein expression correlate significantly with ccRCC aggressiveness. APLNR is expressed in tumour vasculature and tumour cells at different levels, and these expression levels associate with tumour aggressiveness in opposing directions. APLNR expression was negatively correlated with PD-L1 expression by tumour cells in a subset of patients with ccRCC. APLNR expression in either compartment is an independent prognostic factor for survival of patients with ccRCC. CONCLUSION: The APLNR/APLN-system appears to play an important role in ccRCC, warranting further clinical investigation.

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Section: Introductionmentioning

confidence: 99%

Apelin and apelin receptor expression in renal cell carcinoma

et al. 2019

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“…Novel therapeutic approaches for RCC are now in clinical trials [ 38 , 39 , 40 ]. The human immune network plays an important role in the identification and subsequent elimination of several types of cancers [ 41 ]. However, the immune network fails to attack metastatic renal cancer.…”

Section: Discussionmentioning

confidence: 99%

Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells

et al. 2020

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Renal cell carcinoma has emerged as one of the leading causes of cancer-related deaths in the USA. Here, we examined the anticancer profile of oxindole derivatives (SH-859) in human renal cancer cells. Targeting 786-O cells by SH-859 inhibited cell growth and affected the protein kinase B/mechanistic target of rapamycin 1 pathway, which in turn downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, as well as other signaling proteins. Treatment with SH-859 altered glycolysis, mitochondrial function, and levels of adenosine triphosphate and cellular metabolites. Flow cytometry revealed the induction of apoptosis and G0/G1 cell cycle arrest in renal cancer cells following SH-859 treatment. Induction of autophagy was also confirmed after SH-859 treatment by acridine orange and monodansylcadaverine staining, immunocytochemistry, and Western blot analyses. Finally, SH-859 also inhibited the tumor development in a xenograft model. Thus, SH-859 can serve as a potential molecule for the treatment of human renal carcinoma.

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“…Several clinical trials demand the development of newer therapeutic approaches for RCC [28,29,30]. The immune system plays a vital role in the recognition and subsequent rejection of several types of cancer [31]. Unfortunately, the immune system is not always adequate in attacking and treating metastatic renal cancer.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma

Dey

Son

Kundu

et al. 2019

IJMS

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Emerging evidence indicates that the activity of pyruvate kinase M2 (PKM2) isoform is crucial for the survival of tumor cells. However, the molecular mechanism underlying the function of PKM2 in renal cancer is undetermined. Here, we reveal the overexpression of PKM2 in the proximal tubule of renal tumor tissues from 70 cases of patients with renal carcinoma. The functional role of PKM2 in human renal cancer cells following small-interfering RNA-mediated PKM2 knockdown, which retarded 786-O cell growth was examined. Targeting PKM2 affected the protein kinase B (AKT)/mechanistic target of the rapamycin 1 (mTOR) pathway, and downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, and other downstream signaling key proteins. PKM2 knockdown changed glycolytic metabolism, mitochondrial function, adenosine triphosphate (ATP) level, and intracellular metabolite formation and significantly reduced 786-O cell migration and invasion. Acridine orange and monodansylcadaverine staining, immunocytochemistry, and immunoblotting analyses revealed the induction of autophagy in renal cancer cells following PKM2 knockdown. This is the first study to indicate PKM2/AKT/mTOR as an important regulatory axis mediating the changes in the metabolism of renal cancer cells.

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The current status of immunobased therapies for metastatic renal-cell carcinoma

Cited by 15 publications

References 91 publications

Apelin and apelin receptor expression in renal cell carcinoma

Apelin and apelin receptor expression in renal cell carcinoma

Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells

Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma

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