Restoring ASPP1 May Improve Outcomes in Clear Cell RCC

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Downregulation of apoptosis stimulating of p53 protein 1 confers drug resistance and permits tumor growth in clear cell renal cell carcinoma.
Downregulation of apoptosis stimulating of p53 protein 1 confers drug resistance and permits tumor growth in clear cell renal cell carcinoma.

Downregulation of apoptosis stimulating of p53 protein1 (ASPP1) confers drug resistance and permits tumor growth in clear cell renal cell carcinoma (ccRCC), according to an article published in the International Journal of Cancer.1

p53 mutation correlates with cancer drug resistance, though this gene is rarely inactivated in ccRCC, though chemotherapy resistance is a hallmark of this disease. Non-genetic means of inactivating p53 may be responsible.

For this study, researchers evaluated the role of ASPP1 in p53­-related tumor cell apoptosis by comparing ccRCC tissue samples from 20 patients against normal tissue samples.

Compared with normal tissue, the average ASPP1 microRNA transcripts were downregulated 3.9-fold and the protein level was downregulated by 4.9-fold. More than 95% with ccRCC had “remarkably” decreased ASPP1 levels, regardless of age and sex.

ASPP1 downregulation was also directly associated with worse disease stage and prognosis.

The authors noted that ASPP1 downregulation was not confined to the clear cell subtype, and was also found in sarcomatoid and papillary RCC.

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Restoring ASPP1 expression suppressed ccRCC growth and conferred sensitivity to fluorouracil.

The authors concluded that “further investigation is warranted to ascertain if ASPP1 could be a useful prognostic factor or therapeutic target in ccRCC and many others.”

Reference

  1. Wang X, Cheng Y, Zhu Y, et al. Epigenetic silencing of ASPP1 confers 5-FU resistance in clear cell renal cell carcinoma by preventing p53 activation. Int J Cancer. 2017 Jun 28. doi: 10.1002/ijc.30852 [Epub ahead of print]

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