The promising role of nivolumab in renal cell cancers

Gupta, Kanika; Tiu, Dorenett Yu; Tiu, John; Aragon‐Ching, Jeanny B.

doi:10.1080/15384047.2016.1139269

Cited by 7 publications

(6 citation statements)

References 4 publications

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“…Immune checkpoint inhibition, including PD‐1/PD‐L1 blockade, greatly improves the prognosis of patients with mRCC. [ 9 ] HIF has been shown to upregulate PD‐L1 on tumor cells; similarly, VEGF upregulates PD‐1 on immune cells, promoting T cell exhaustion in the RCC microenvironment. [ 10 ] Thus, patients with mRCC may benefit from the combination of TKIs with PD‐1/PD‐L1 blockade.…”

Section: Introductionmentioning

confidence: 99%

RRM2 Regulates Sensitivity to Sunitinib and PD‐1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway

Wang

Zhang

et al. 2021

Advanced Science

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Renal cell carcinoma (RCC) is a malignant tumor of the kidneys.Approximately 70% of RCC cases are clear cell renal cell carcinoma with von Hippel-Lindau (VHL) gene mutation and activation of the vascular endothelial growth factor (VEGF) pathway. Tyrosine kinase inhibitors (TKIs) targeting VEGF have emerged as promising agents for RCC treatment. Apart from primary resistance, acquired resistance to TKIs after initial tumor regression is common in RCC. Recently, immune checkpoint inhibition, including PD-1/PD-L1 blockade, alone or in combination with TKIs has improved the overall survival of patients with RCC. Ribonucleotide reductase subunit M2 (RRM2) has been reported in many types of cancer and has been implicated in tumor progression. However, the role of RRM2 in TKIs resistance in RCC remains unclear. In this study, the authors have demonstrated that RRM2 is upregulated in sunitinib-resistant RCC cells and patient tissues. They also find that RRM2 stabilizes ANXA1 and activates the AKT pathway independent of its ribonucleotide reductase activity, promoting sunitinib resistance in RCC. Moreover, RRM2 regulated antitumor immune responses, and knockdown of RRM2 enhance the anti-tumor efficiency of PD-1 blockade in renal cancer. Collectively, these results suggest that aberrantly expressed RRM2 may be a promising therapeutic target for RCC.

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Section: Introductionmentioning

confidence: 99%

RRM2 Regulates Sensitivity to Sunitinib and PD‐1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway

Wang

Zhang

et al. 2021

Advanced Science

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“…It is currently approved by the United States Food and Drug Administration for the treatment of various cancers including melanoma, non-small cell lung cancer, and RCC. Of particular relevance to our case, nivolumab has shown a promising role in metastatic RCC [10].…”

Section: Discussionmentioning

confidence: 99%

“…Anti-PD-1 immunotherapy aims to revitalize a suppressed immune response to foreign cancer cells. Multiple studies and clinical trials of nivolumab for various cancers have shown promising results [10-14]. In particular, patients with advanced treatment-refractory RCC have demonstrated durable responses [10,13,14].…”

Section: Discussionmentioning

confidence: 99%

Pneumonitis in Combined Anti-programmed Death-1 Immunotherapy and Radiation Therapy for Renal Cell Carcinoma

Deftos

Wang

2018

Cureus

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“…Consequently, several other treatment modalities including surgical resection (metastasectomy), radiotherapy, and classical immune therapy are still used to extend overall survival (OS) rates [ 7 , 8 ]. Furthermore, we are currently awaiting the approval and availability of the next generation of immune checkpoint inhibitors, which are currently under clinical trials [ 9 - 11 ]. Hence, defining poor responders or those with increased resistance to targeted agents will significantly impact treatment planning outcomes.…”

Section: Introductionmentioning

confidence: 99%

Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents

et al. 2017

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BackgroundTo assess the prognostic and predictive factors of time to treatment failure (TTF) and overall survival (OS), respectively, in patients with metachronous metastatic renal cell carcinoma (mRCC) who were treated with targeted agents.Materials and MethodsWe retrospectively reviewed metachronous mRCC patients, defined as individuals diagnosed with metastatic disease >3 months after initial nephrectomy, treated at an institute since 2005. Cox proportional hazard regression analysis was performed to discover the most determinant variables associated with TTF and OS.ResultsSarcomatoid features, absence of metastasectomy, multiple site metastasis, time to metastasis <1.5 year, and increased corrected calcium were independent prognostic factors of OS. The low risk group (0–1 risk factors) did not reach the median OS, whereas the OS for the intermediate (2 risk factors) and high risk groups (3–5 risk factors) were 58.6 and 23.6 months, respectively (p<0.001). When a death event was considered the dependent factor, the area under the receiver operating characteristic curve was significantly higher than in the existing International mRCC Database Consortium (IMDC; p=0.010) and Memorial Sloan Kettering Cancer Center (MSKCC; p=0.010) risk criteria models.ConclusionInitial tumor size or T stage did not affect TTF or OS. Patients who could not undergo metastasectomy and rapidly developed multiple metastases with higher corrected calcium and initial tumors with sarcomatoid features were less likely to benefit from targeted therapy; thus, the new agents under development or clinical trials could be more helpful than the use of standard targeted agents.

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The promising role of nivolumab in renal cell cancers

Cited by 7 publications

References 4 publications

RRM2 Regulates Sensitivity to Sunitinib and PD‐1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway

RRM2 Regulates Sensitivity to Sunitinib and PD‐1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway

Pneumonitis in Combined Anti-programmed Death-1 Immunotherapy and Radiation Therapy for Renal Cell Carcinoma

Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents

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