Treatment of renal cell carcinoma: Current status and future directions

Barata, Pedro C.; Rini, Brian I.

doi:10.3322/caac.21411

Cited by 619 publications

(540 citation statements)

References 142 publications

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“…The emergence of immune checkpoint inhibition as a front‐line therapeutic strategy for metastatic RCC has also heralded investigation of these agents as potential adjuvant agents. The biological rationale is that Th1 immune‐related response to tumors can be enhanced by blocking the immune cell‐specific inhibitory pathways, namely the PD‐1 receptor and PDL‐1 . Currently, there are four clinical trials examining the potential of checkpoint inhibitors in localized RCC to reduce the risk of recurrence: atezolizumab (one trial, NCT03024996), combination nivolumab and ipilimumab (one trial, NCT03138512), pembrolizumab (one trial, NCT03142334), and durvalumab monotherapy or in combination with tremelimumab (NCT03288532)…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives

et al. 2019

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Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high‐risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron‐sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double‐blind placebo‐controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma.

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives

et al. 2019

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“…Renal clear cell carcinoma (KIRC), renal papillary cell carcinoma (KIRP) and chromophobe carcinoma (KICH) are the most common RCC . Despite advances in diagnosis, screening, surgery and drug therapy, the clinical outcome of RCC remains unsatisfactory . As a well‐known heterogeneous disease, the useful biomarkers which contribute to individualized treatment options are still lacking for RCC, especially in current immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Immune infiltration in renal cell carcinoma

et al. 2019

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Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma ( RCC ). Tumor‐infiltrating immune cells ( TIIC s) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIIC s in RCC and further reveal the independent prognostic values of TIIC s. CIBERSORT , an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIIC s and immune checkpoint modulators with overall survival ( OS ). We found that CD 8+ T cells were associated with prolonged OS (hazard ratio [ HR ] = 0.09, 95% confidence interval [ CI ].01‐.53; P = 0.03) in chromophobe carcinoma ( KICH ). A higher proportion of regulatory T cells was associated with a worse outcome ( HR = 1.59, 95% CI 1.23‐.06; P < 0.01) in renal clear cell carcinoma ( KIRC ). In renal papillary cell carcinoma ( KIRP ), M1 macrophages were associated with a favorable outcome ( HR = .43, 95% CI .25‐.72; P < 0.01), while M2 macrophages indicated a worse outcome ( HR = 2.55, 95% CI 1.45‐4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA 4 and LAG 3 were associated with a poor prognosis in KIRC , and IDO 1 and PD ‐L2 were associated with a poor prognosis in KIRP . This study indicates TIIC s are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development.

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“…Renal cancer is one of the most common malignant cancers . Despite the continuous progress in medical treatment, the incidence of the disease has increased year by year . There are many types of renal cancer according to histopathologic and cell features.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of long noncoding RNA associated‐competing endogenous RNA as prognostic biomarkers in clear cell renal carcinoma

et al. 2018

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Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant carcinomas and its molecular mechanisms remain unclear. Long noncoding RNA (lncRNA) could bind sites of miRNA which affect the expression of mRNA according to the competing endogenous (ceRNA) theory. The aim of the present study was to construct a ceRNA network and to identify key lncRNA to predict survival prognosis. We identified differentially expressed mRNA, lncRNA and miRNA between tumor tissues and normal tissues from The Cancer Genome Atlas database. Then, using bioinformatics tools, we explored the connection of 89 lncRNA, 10 miRNA and 22 mRNA, and we constructed the ceRNA network. Furthermore, we analyzed the functions and pathways of 22 differentially expressed mRNA. Then, univariate and multivariate Cox regression analyses of these 89 lncRNA and overall survival were explored. Nine lncRNA were finally screened out in the training group. The patients were divided into high‐risk and low‐risk groups according to the 9 lncRNA and low‐risk scores having better clinical overall survival (P < .01). Furthermore, the receiver operating characteristic curve demonstrates the predicted role of the 9 lncRNA. The 9‐lncRNA signature was successfully proved in the testing group and the entire group. Finally, multivariate Cox regression analysis and stratification analysis further proved that the 9‐lncRNA signature was an independent factor to predict survival. In summary, the present study provides a deeper understanding of the lncRNA‐related ceRNA network in ccRCC and suggests that the 9‐lncRNA signature could serve as an independent biomarker to predict survival in ccRCC patients.

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Treatment of renal cell carcinoma: Current status and future directions

Cited by 619 publications

References 142 publications

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives

Immune infiltration in renal cell carcinoma

Integrated analysis of long noncoding RNA associated‐competing endogenous RNA as prognostic biomarkers in clear cell renal carcinoma

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