Is small cell lung cancer the perfect target for anti- telomerase treatment?

Small cell lung cancer (SCLC) is common in men and women, has<SUP> </SUP>a very poor prognosis, and is therefore a major cause of premature<SUP> </SUP>mortality. As such, any prospects for improved therapy are of<SUP> </SUP>great significance. The promise of telomerase as a therapeutic<SUP> </SUP>target is now close to realization with extremely encouraging<SUP> </SUP>preclinical studies aimed at the RNA component (hTR) of telomerase.<SUP> </SUP>The rational integration of telomerase therapeutics into clinical<SUP> </SUP>trials will therefore require tumours to be well characterized<SUP> </SUP>for hTR expression. Despite the large number of cancer types<SUP> </SUP>now characterized for telomerase or telomerase component gene<SUP> </SUP>expression, only a handful of SCLC samples have been analysed.<SUP> </SUP>Given the major clinical problem with treating SCLC, we specifically<SUP> </SUP>set out to address the issue of hTR expression in neuroendocrine<SUP> </SUP>tumours. Our study covers 91 pulmonary neuroendocrine tumours<SUP> </SUP>(62 SCLC and 29 carcinoid tumours). We present data to show<SUP> </SUP>that upregulation of the RNA component of telomerase occurs<SUP> </SUP>in 98% of human SCLCs. Interestingly, the less aggressive carcinoid<SUP> </SUP>tumours of the lung had a significantly lower frequency of hTR<SUP> </SUP>expression (<I>P</I> < 0.01). Importantly, we compare hTR expression<SUP> </SUP>in this series to the well characterized biological targets<SUP> </SUP>p53 and BCL2, and show hTR to be expressed more frequently.<SUP> </SUP>Therapies directed at the RNA component of human telomerase<SUP> </SUP>are in active development and these data show SCLC to be a prime<SUP> </SUP>target for such therapies