Metastasis in renal cell carcinoma: Biology and implications for therapy

Gong, Jun; Maia, Manuel Caitano; Dizman, Nazlı; Govindarajan, Ameish; Pal, Sumanta K.

doi:10.1016/j.ajur.2016.08.006

Cited by 120 publications

(139 citation statements)

References 42 publications

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“…Whereas the vast majority of patients where white, we did note a relatively high proportion of Asian patients in many of the low-BMI subgroups, which could reflect the impact of cultural differences in diet or exercise habits on body weight [22]. The distribution of histologic subtypes and metastasis was consistent with past studies [9,23], and thus our study cohort appears representative of the broader RCC patient population recruited in empirical studies.…”

Section: Discussionsupporting

confidence: 79%

Targeted Therapy and Immunotherapy: Effect of Body Mass Index on Clinical Outcomes in Patients Diagnosed with Metastatic Renal Cell Carcinoma

Bergerot

Philip

et al. 2019

KCA

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Background: Previous research has identified an association between high body mass index (BMI) and better overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs). Objective: The current study sought to determine whether the effect of BMI on OS extends beyond VEGF-TKIs to mTOR inhibitors or immunotherapy (IO). Design, Setting and Participants: A retrospective study was conducted among patients diagnosed with mRCC treated at a single institution from 2009 to 2017. Demographic and clinical variables were collected. BMI was characterized as high (≥25 kg/m 2) versus low (<25 kg/m 2). Outcomes Measurement and Statistical Analysis: The Kaplan-Meier method was used to estimate the difference in OS, with comparisons based on BMI and by treatment type. Results and Limitations: Among 353 patients (M = 64 years old, 73% male) 66% were overweight or obese (BMI ≥ 25 kg/m 2). Patients were treated with VEGF-TKI (65%), mTOR (23%), or IO (12%). Among patients treated with VEGF-TKI with low BMI, median OS was 24.0 months (95% CI, 20.7-27.2) versus 36.0 months (95% CI, 18.6-53.3) among patients with high BMI (P = 0.02). The median OS for patients with low BMI treated with mTOR was 18.0 months (95% CI, 2.8-33.1), versus 25.0 months (95% CI, 16.6-33.4) among patients with high BMI (P = 0.04). In contrast, patients with low BMI treated with IO had a median OS of 23.6 months (95% CI, 17.5-29.7) versus 19.9 months (95% CI, 10.6-29.2) among patients with high BMI (P = 0.26). The retrospective nature and the small sample size are the main limitations of this study. Conclusions: High-BMI was associated with improved OS in patients with mRCC treated with VEGF-TKI and mTOR, but the inverse trend was observed among patients receiving IO. Our data highlight the need to reassess this phenomenon in the context of IO-based regimens.

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Section: Discussionsupporting

confidence: 79%

Targeted Therapy and Immunotherapy: Effect of Body Mass Index on Clinical Outcomes in Patients Diagnosed with Metastatic Renal Cell Carcinoma

Bergerot

Philip

et al. 2019

KCA

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“…Renal cell carcinoma (RCC) accounts for more than 90% of renal malignancies and 3.79% of all adult malignancies; RCC arises from renal tubular epithelial cells and is one of the most lethal urological malignancies, with estimated 65 340 new cases and 14 970 deaths in 2018 in the United States . In addition to abnormal glycogen metabolism, clear cell renal cell carcinoma (ccRCC) is characterized by an immense accumulation of lipid in the cytoplasm and has a high rate of mortality, invasion, and metastasis . Additionally, obesity, diabetes, and atherosclerosis have been identified as risk factors for RCC, and renal cancer is considered a metabolic disease; however, the molecular mechanisms and significance of abnormal lipid metabolism remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Melatonin/PGC1A/UCP1 promotes tumor slimming and represses tumor progression by initiating autophagy and lipid browning

Xiao

Zhang

Xiong

et al. 2019

Journal of Pineal Research

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Metabolic adaptations are emerging hallmarks of cancer progression and cellular transformation. Clear cell renal cell carcinoma (ccRCC) is a metabolic disease defined histologically by lipid accumulation and lipid storage, which promote tumor cell survival; however, the significance of eliminating the lipid remains unclear.Here, we demonstrate that melatonin activates transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1A (PGC1A) and uncoupling protein 1 (UCP1)-dependent lipid autophagy and a lipid browning program to elicit a catabolic state called "tumor slimming," thus suppressing tumor progression.Metabolic coregulator data analysis revealed that PGC1A expression was decreased in ccRCC tissues versus normal tissues, and poor patient outcome was associated with lower expression of PGC1A in The Cancer Genome Atlas (TCGA-KIRC).PGC1A was downregulated in ccRCC and associated with disease progression.Restoration of PGC1A expression by melatonin in ccRCC cells significantly repressed tumor progression and eliminated the abnormal lipid deposits. Furthermore, a phenomenon called "tumor slimming" was observed, in which tumor cell volume was reduced and lipid droplets transformed into tiny pieces. Additional studies indicated that melatonin promoted "tumor slimming" and suppressed ccRCC progression through PGC1A/UCP1-mediated autophagy and lipid browning. During this process, autophagy and lipid browning eliminate lipid deposits without providing energy. These studies demonstrate that the novel "tumor slimming" pathway mediated by melatonin/PGC1A/UCP1 exhibits prognostic potential in ccRCC, thus revealing the significance of monitoring and manipulating this pathway for cancer therapy. K E Y W O R D Sautophagy, lipid browning, melatonin, PGC1A, tumor slimming, UCP1 2 of 18 | XIAO et Al.

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“…At present, there is no defined role for adjuvant therapy for localized RCC following partial or radical nephrectomy. The current standard of care involves serial imaging with CT, typically up to a span of 5 years [14].…”

Section: Discussionmentioning

confidence: 99%

Cutaneous metastatic renal cell carcinoma to the scalp

Yang

Kang

2019

Arch Craniofac Surg

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Renal cell carcinoma (RCC) represents 2% to 3% of human cancers and is aggressive, with metastatic capability. The frequent metastatic sites are lung, bone, and liver. Reports of RCC metastatic to skin, and especially scalp are rare. Here we present an 83-year-old woman who was diagnosed with RCC 19 years prior and had a metastatic scalp lesion. An 83-year-old woman presented with a red-to-purple, protruding lesion at the right parietotemporal area. Twenty-three years ago, a right renal mass was incidentally discovered on ultrasound through a routine medical examination. She underwent right nephrectomy for RCC 4 years later. Five months after nephrectomy, new lung nodules were observed. Fifteen years after nephrectomy, metastatic lesions were found in the pelvic bone. She visited dermatology department for evaluation of the new scalp lesion, a year before she first visited our department. Despite chemotherapy, the mass was gradually enlarged. She consulted the plastic surgery department for management of the metastatic RCC was successfully treated with total excision including a 1-cm safety margin, local flap, and STSG coverage. Complete healing was observed, without evidence of recurrence during a 7-month followup. Metastases to the skin are rare, but must be kept in mind because of its high metastatic ability and poor prognosis.

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Metastasis in renal cell carcinoma: Biology and implications for therapy

Cited by 120 publications

References 42 publications

Targeted Therapy and Immunotherapy: Effect of Body Mass Index on Clinical Outcomes in Patients Diagnosed with Metastatic Renal Cell Carcinoma

Targeted Therapy and Immunotherapy: Effect of Body Mass Index on Clinical Outcomes in Patients Diagnosed with Metastatic Renal Cell Carcinoma

Melatonin/PGC1A/UCP1 promotes tumor slimming and represses tumor progression by initiating autophagy and lipid browning

Cutaneous metastatic renal cell carcinoma to the scalp

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