In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 1169-1169
Abstract:
Renal medullary carcinoma (RMC) is a rare and aggressive disease that predominantly afflicts individuals of African or Mediterranean descent with sickle cell trait. RMC comprises 1% of all renal cell carcinoma diagnoses, and the median overall survival for RMC patients is only 13 months. Patients are typically young (median age-22yo) and male (male:female ratio of 2:1). RMC was first characterized in 1995, and its hallmark SMARCB1 loss was identified in 2008. Due to the low incidence of RMC and the disease's aggressiveness, treatment decisions are often based on case reports. Thus, it is critical to develop preclinical models of RMC to both better understand the pathogenesis of this disease and identify an effective therapy. These RMC cell lines overexpress EZH2, relative to normal renal proximal tubule epithelium, thus making it an attractive druggable target. EZH2 inhibition in RMC tumor spheroids did not result in decreased viability. We have evaluated a potential clinical treatment (bortezomib) found in the literature and validate bortezomib's potency in vitro. Intriguingly, these cells lines not only lack NQO1, an antioxidant enzyme, but also the addition of N-acetyl cysteine, an antioxidant, has a protective effect against bortezomib. Together the data suggest that RMC are highly sensitive to oxidative stress. This evidence is consistent with case reports in the literature that found bortezomib treatment of RMC resulted in positive outcomes. Citation Format: Darmood Wei, Youfeng Yang, Christopher J. Ricketts, Cathy D. Vocke, Mark W. Ball, Carole Sourbier, Darawalee Wangsa, Danny Wangsa, Rajarshi Guha, Xiaohu Zhang, Paul Meltzer, Thomas Reid, Craig J. Thomas, Maria J. Merino, W. Marston Linehan. Novel renal medullary carcinoma cell lines, UOK353 and UOK360, provide preclinical tools to identify new therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1169.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-1169
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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