Image-guided Cryoablation for Sporadic Renal Cell Carcinoma: Is It Time to Revisit the Standard of Care for Small Renal Tumors?

Cathepsin K is a papain-like cysteine protease with high matrix-degrading activity. Among several cathepsins, cathepsin K is the most potent mammalian collagenase, mainly expressed by osteoclasts. This review summarizes most of the recent findings of cathepsin K expression, highlighting its role in renal tumors for diagnostic purposes and as a potential molecular target. Indeed, cathepsin K is a recognized diagnostic tool for the identification of TFE3/TFEB-rearranged renal cell carcinoma, TFEB-amplified renal cell carcinoma, and pure epithelioid PEComa/epithelioid angiomyolipoma. More recently, its expression has been observed in a subgroup of eosinophilic renal neoplasms molecularly characterized by TSC/mTOR gene mutations. Interestingly, both TSC mutations or TFE3 rearrangement have been reported in pure epithelioid PEComa/epithelioid angiomyolipoma. Therefore, cathepsin K seems to be a downstream marker of TFE3/TFEB rearrangement, TFEB amplification, and mTOR pathway activation. Given the established role of mTOR inhibitors as a pharmacological option in renal cancers, cathepsin K could be of use as a predictive marker of therapy response and as a potential target. In the future, uropathologists may implement the use of cathepsin K to establish a diagnosis among renal tumors with clear cells, papillary architecture, and oncocytic features.

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The DEAD/DEAH Box Helicase, DDX11, Is Essential for the Survival of Advanced Clear Cell Renal Cell Carcinoma and Is a Determinant of PARP Inhibitor Sensitivity

Cancers ◽

10.3390/cancers13112574 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2574

Author(s):

Jee Soo Park ◽

Myung Eun Lee ◽

Won Sik Jang ◽

Koon Ho Rha ◽

Seung Hwan Lee ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Quantitative Polymerase Chain Reaction ◽

Parp Inhibitor ◽

Renal Tumors ◽

Low Grade ◽

Normal Kidney ◽

The Dead ◽

The Impact

Genes associated with the DEAD-box helicase DDX11 are significant biomarkers of aggressive renal cell carcinoma (RCC), but their molecular function is poorly understood. We analyzed the molecular pathways through which DDX11 is involved in RCC cell survival and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Immunohistochemistry and immunoblotting determined DDX11 expression in normal kidney tissues, benign renal tumors, and RCC tissues and cell lines. Quantitative polymerase chain reaction validated the downregulation of DDX11 in response to transfection with DDX11-specific small interfering RNA. Proliferation analysis and apoptosis assays were performed to determine the impact of DDX11 knockdown on RCC cells, and the relevant effects of sunitinib, olaparib, and sunitinib plus olaparib were evaluated. DDX11 was upregulated in high-grade, advanced RCC compared to low-grade, localized RCC, and DDX11 was not expressed in normal kidney tissues or benign renal tumors. DDX11 knockdown resulted in the inhibition of RCC cell proliferation, segregation defects, and rapid apoptosis. DDX11-deficient RCC cells exhibited significantly increased sensitivity to olaparib compared to sunitinib alone or sunitinib plus olaparib combination treatments. Moreover, DDX11 could determine PARP inhibitor sensitivity in RCC. DDX11 could serve as a novel therapeutic biomarker for RCC patients who are refractory to conventional targeted therapies and immunotherapies.

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Another Milestone for Cryoablation on Its Way to Becoming the Standard of Care for Stage T1A Renal Cell Carcinoma

Radiology ◽

10.1148/radiol.2020202037 ◽

2020 ◽

Vol 296 (3) ◽

pp. 696-697

Author(s):

Christos S. Georgiades

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Standard Of Care

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Sporadic renal cell carcinoma in young adults: presentation, treatment, and outcome

Urology ◽

10.1016/s0090-4295(02)01884-8 ◽

2002 ◽

Vol 60 (5) ◽

pp. 806-810 ◽

Cited By ~ 35

Author(s):

Hazem I Abou El Fettouh ◽

Edward E Cherullo ◽

Mohamed El-Jack ◽

Youssef Al Maslamani ◽

Andrew C Novick

Keyword(s):

Renal Cell Carcinoma ◽

Young Adults ◽

Cell Carcinoma ◽

Renal Cell ◽

Sporadic Renal Cell Carcinoma

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The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma

Therapeutic Advances in Urology ◽

10.1177/1756287217732660 ◽

2017 ◽

Vol 10 (1) ◽

pp. 3-10 ◽

Cited By ~ 1

Author(s):

Reza Mehrazin ◽

Essel Dulaimi ◽

Robert G. Uzzo ◽

Karthik Devarjan ◽

Jianming Pei ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Cytogenetic Analysis ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Renal Tumors ◽

Rank Test

Background: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. Results: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( n = 11) or CMA ( n = 7). Gain of 8q was associated with higher T stage ( p < 0.001), grade ( p < 0.001), nodal involvement ( p = 0.005), and distant metastasis ( p < 0.001). No association between gain of 8q and age ( p = 0.23), sex ( p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83–18.34, p < 0.001] and 3.31-fold (95% CI, 1.56–7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.

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Preclinical activity of cobimetinib alone or in combination with chemotherapy and targeted therapies in renal cell carcinoma

Future Oncology ◽

10.2217/fon-2021-0256 ◽

2021 ◽

Author(s):

Lichen Zhang ◽

Deqiong Xie ◽

Yonghua Lei ◽

Aoli Na ◽

Lei Zhu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Mapk Pathway ◽

Standard Of Care ◽

Underlying Mechanism ◽

Mek Inhibitor ◽

Tumor Formation ◽

Pathway Inhibition ◽

New Treatments

Background: The poor outcome of advanced renal cell carcinoma (RCC) necessitates new treatments. Cobimetinib is a MEK inhibitor and approved for the treatment of melanoma. This work investigated the efficacy of cobimetinib alone and in combination with anti-RCC drugs. Methods: Proliferation and apoptosis assays were performed, and combination index was analyzed on RCC cell lines (CaKi-2, 786-O, A-704, ACHN and A489) and xenograft models. Immunoblotting analysis was conducted to investigate the MAPK pathway. Results: Cobimetinib was active against RCC cells, with IC50 at 0.006–0.8μM, and acted synergistically with standard-of-care therapy. Cobimetinib at nontoxic doses prevented tumor formation, inhibited tumor growth and enhanced efficacy of 5-fluorouracil, sorafenib and sunitinib via suppressing Raf/MEK/ERK, leading to MAPK pathway inhibition. Conclusion: Our findings demonstrate the potent anti-RCC activity of cobimetinib and its synergism with RCC standard-of-care drugs, and confirm the underlying mechanism of the action of cobimetinib.

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Childhood renal cell carcinoma

Paediatrica Indonesiana ◽

10.14238/pi46.2.2006.93-6 ◽

2016 ◽

Vol 46 (2) ◽

pp. 93

Author(s):

Nouval Shahab ◽

Arry Rodjani ◽

Rainy Umbas

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Renal Tumors ◽

First Report ◽

The Third ◽

Knowl Edge ◽

First Case

Renal cell carcinoma (RCC) in children isseldom found. The incidence of thistumor in childhood is estimated to be 0.1-0.3% out of all neoplasms and 2-7% out ofall malignant renal tumors. The Third NationalCancer Survey reported an incidence of only four casesof RCC per year compared to 117 per year of Wilms’tumor.The incidence of RCC has not been reported inIndonesia. This is the first case of childhood RCCfound in our institution. To the best of our knowl-edge, this is the first report of childhood RCC in In-donesia.

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Safety and oncological outcomes for large (stage ≥T2b) and locally advanced renal cell carcinoma: comparison between laparoscopic and modified hand-assisted laparoscopic radical nephrectomy

Journal of International Medical Research ◽

10.1177/0300060520961238 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052096123

Author(s):

Xudong Guo ◽

Hanbo Wang ◽

Yuzhu Xiang ◽

Xunbo Jin ◽

Shaobo Jiang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Radical Nephrectomy ◽

Locally Advanced ◽

Survival Rates ◽

Renal Tumors ◽

Advanced Renal Cell Carcinoma ◽

Operative Duration ◽

Laparoscopic Radical Nephrectomy

Objective To compare the operative and oncologic outcomes between hand-assisted laparoscopic radical nephrectomy (HALRN) and laparoscopic radical nephrectomy (LRN) for large (stage ≥T2b) and locally advanced renal cell carcinoma. Methods We retrospectively collected data from patients who underwent HALRN or LRN for stage ≥T2b renal cell carcinoma from January 2011 to January 2018 in our institution. The patients’ demographics, perioperative parameters, and postoperative follow-up data were compared between the two groups. The survival outcome was estimated using the Kaplan–Meier method. Results The HALRN group comprised 78 patients, and the LRN group comprised 63 patients. The median operative duration was significantly shorter in the HALRN than LRN group. The two groups were equivalent in terms of the incision length, blood loss, complication rate, and duration of hospitalization. In the HALRN and LRN groups, the 5-year overall survival rates were 69.4% and 73.1%, the 5-year cancer-specific survival rates were 80.0% and 83.3%, and the 5-year progression-free survival rates were 66.4% and 74.7%, respectively, with no significant differences. Conclusions Compared with LRN, HALRN may offer a shorter operative duration and equivalent surgical outcomes without sacrificing oncological efficacy. In addition, HALRN has specific advantages for extremely large and complicated renal tumors.

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