Combination therapies in clinical trials for renal cell carcinoma: how could they impact future treatments?

Ince, Will; Eisen, Tim

doi:10.1080/13543784.2021.2014814

Cited by 4 publications

(3 citation statements)

References 70 publications

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“…While the survival rate of mccRCC patients is undoubtedly increased by the combination of classical clinical therapies, fully durable responses are rare currently ( 82 ). Additionally, combined therapies have limited effects on patients who are insensitive to anti-angiogenic therapies and have failed ICI treatment ( 83 ).…”

Section: Classical Clinical Treatmentsmentioning

confidence: 99%

Treatment strategies for clear cell renal cell carcinoma: Past, present and future

2023

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Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, which is prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy. The burden it places on human health due to its refractory nature and rising incidence rate is substantial. Researchers have recently determined the ccRCC risk factors and optimized the clinical therapy based on the disease’s underlying molecular mechanisms. In this paper, we review the established clinical therapies and novel potential therapeutic approaches for ccRCC, and we support the importance of investigating novel therapeutic options in the context of combining established therapies as a research hotspot, with the goal of providing diversified therapeutic options that promise to address the issue of drug resistance, with a view to the early realization of precision medicine and individualized treatment.

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Section: Classical Clinical Treatmentsmentioning

confidence: 99%

Treatment strategies for clear cell renal cell carcinoma: Past, present and future

2023

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“…They can enhance the inhibition of cell proliferation and cell growth, and also enhance the inhibition of angiogenesis in cancers ( Rausch et al, 2020 ; Sharma et al, 2021 ). However, combination therapies may cause undesirable drug interactions and unnecessary drug toxicity ( Zou et al, 2019 ; Ince and Eisen, 2021 ). To avoid the mentioned problem, we intend to combine HDAC1 with other targets to develop dual-targeting inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel and potent dual-targeting HDAC1/SPOP inhibitors using structure-based virtual screening, molecular dynamics simulation and evaluation of in vitro and in vivo antitumor activity

et al. 2023

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Cancer is one of the important factors threatening human health. Hence, it is essential to create novel potent drugs to treat it. Due to the strong correlation among histone deacetylase1 (HDAC1), speckle-type POZ protein (SPOP) and cancers, dual inhibition of HDAC1 and SPOP may be a promising strategy for cancer treatment. In this study, we successfully identified four potential dual-targeting HDAC1/SPOP candidate compounds with structure-based virtual screening. In vitro inhibition experiments confirmed that the four compounds had dual inhibitory effects on HDAC1 and SPOP. Among them, compound HS-2 had a stronger inhibitory effect on HDAC1 and SPOP than the positive controls. Further molecular dynamics simulations indicated that HS-2 could stably bind to HDAC1 and SPOP. In addition, MTT assay indicated that HS-2 inhibited the growth of tumor cells in the micromolar range. In vivo evaluation showed that HS-2 could obviously inhibit the growth of tumor in nude mice without obvious toxicity. These findings suggest that HS-2 is a novel and potent dual-targeting HDAC1/SPOP inhibitor for cancer treatment.

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“…Notably, the prognosis of metastatic RCC patients is still poor, with the 5-years survival rate remaining at 10–15%. Thus, there is an urgent need to find reliable biomarkers to predict RCC patient outcomes ( Kabaria et al, 2016 ; Reed et al, 2019 ; Lee et al, 2021a ; Bedke et al, 2021 ; Doppalapudi et al, 2021 ; Ince and Eisen, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A Cluster of Metabolic-Related Genes Serve as Potential Prognostic Biomarkers for Renal Cell Carcinoma

et al. 2022

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Renal cell carcinoma (RCC) is the most common type of renal cancer, characterized by the dysregulation of metabolic pathways. RCC is the second highest cause of death among patients with urologic cancers and those with cancer cell metastases have a 5-years survival rate of only 10–15%. Thus, reliable prognostic biomarkers are essential tools to predict RCC patient outcomes. This study identified differentially expressed genes (DEGs) in the gene expression omnibus (GEO) database that are associated with pre-and post-metastases in clear cell renal cell carcinoma (ccRCC) patients and intersected these with metabolism-related genes in the Kyoto encyclopedia of genes and genomes (KEGG) database to identify metabolism-related DEGs (DEMGs). GOplot and ggplot packages for gene ontology (GO) and KEGG pathway enrichment analysis of DEMGs with log (foldchange) (logFC) were used to identify metabolic pathways associated with DEMG. Upregulated risk genes and downregulated protective genes among the DEMGs and seven independent metabolic genes, RRM2, MTHFD2, AGXT2, ALDH6A1, GLDC, HOGA1, and ETNK2, were found using univariate and multivariate Cox regression analysis, intersection, and Lasso-Cox regression analysis to establish a metabolic risk score signature (MRSS). Kaplan-Meier survival curve of Overall Survival (OS) showed that the low-risk group had a significantly better prognosis than the high-risk group in both the training cohort (p < 0.001; HR = 2.73, 95% CI = 1.97–3.79) and the validation cohort (p = 0.001; HR = 2.84, 95% CI = 1.50–5.38). The nomogram combined with multiple clinical information and MRSS was more effective at predicting patient outcomes than a single independent prognostic factor. The impact of metabolism on ccRCC was also assessed, and seven metabolism-related genes were established and validated as biomarkers to predict patient outcomes effectively.

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Combination therapies in clinical trials for renal cell carcinoma: how could they impact future treatments?

Cited by 4 publications

References 70 publications

Treatment strategies for clear cell renal cell carcinoma: Past, present and future

Treatment strategies for clear cell renal cell carcinoma: Past, present and future

Identification of novel and potent dual-targeting HDAC1/SPOP inhibitors using structure-based virtual screening, molecular dynamics simulation and evaluation of in vitro and in vivo antitumor activity

A Cluster of Metabolic-Related Genes Serve as Potential Prognostic Biomarkers for Renal Cell Carcinoma

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