AI Article Synopsis
- * Research using patient-derived xenografts revealed that chemoresistant models showed decreased levels of SLFN11, which is important for repairing DNA damage.
- * Combining an EZH2 inhibitor with conventional chemotherapy can prevent the development of resistance and enhance treatment effectiveness in both responsive and resistant lung cancer models.
Article Abstract
Small cell lung cancer is initially highly responsive to cisplatin and etoposide but in almost every case becomes rapidly chemoresistant, leading to death within 1 year. We modeled acquired chemoresistance in vivo using a series of patient-derived xenografts to generate paired chemosensitive and chemoresistant cancers. Multiple chemoresistant models demonstrated suppression of SLFN11, a factor implicated in DNA-damage repair deficiency. In vivo silencing of SLFN11 was associated with marked deposition of H3K27me3, a histone modification placed by EZH2, within the gene body of SLFN11, inducing local chromatin condensation and gene silencing. Inclusion of an EZH2 inhibitor with standard cytotoxic therapies prevented emergence of acquired resistance and augmented chemotherapeutic efficacy in both chemosensitive and chemoresistant models of small cell lung cancer.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313262 | PMC |
| http://dx.doi.org/10.1016/j.ccell.2017.01.006 | DOI Listing |
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