Is small cell lung cancer the perfect target for anti-telomerase treatment?
Small cell lung cancer (SCLC) is common in men and women, has a very poor prognosis, and is therefore a major cause of premature mortality. As such, any prospects for improved therapy are of great significance. The promise of telomerase as a therapeutic target is now close to realization with extremely encouraging preclinical studies aimed at the RNA component (hTR) of telomerase. The rational integration of telomerase therapeutics into clinical trials will therefore require tumours to be well characterized for hTR expression. Despite the large number of cancer types now characterized for telomerase or telomerase component gene expression, only a handful of SCLC samples have been analysed. Given the major clinical problem with treating SCLC, we specifically set out to address the issue of hTR expression in neuroendocrine tumours. Our study covers 91 pulmonary neuroendocrine tumours (62 SCLC and 29 carcinoid tumours). We present data to show that upregulation of the RNA component of telomerase occurs in 98% of human SCLCs. Interestingly, the less aggressive carcinoid tumours of the lung had a significantly lower frequency of hTR expression (P < 0.01). Importantly, we compare hTR expression in this series to the well characterized biological targets p53 and BCL2, and show hTR to be expressed more frequently. Therapies directed at the RNA component of human telomerase are in active development and these data show SCLC to be a prime target for such therapies.
Sarvesvaran
J
J
CRC Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Going
J J
JJ
Milroy
R
R
Kaye
S B
SB
Keith
W N
WN
D002276:Carcinoid Tumor / Q000201:enzymology* / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D012313:RNA; D019098:Telomerase