European Journal of Cancer: Highlights of Issue 38:17

Opening the door to novel therapeutic targets for rhabdomyosarcomas

Moretti and colleagues show in this issue that differing levels of two cyclin-dependent kinase inhibitors (cdkIs), p21 and p27, could determine outcome in paediatric rhabdomyosarcomas (RMS). They examined two types of RMS, embryonal (ERMS) and alveolar (ARMS) rhabdomyosarcomas, by the reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical assays and showed that ERMS, that have a better prognosis, had much higher levels of p21 and p27. They also treated 2 RMS cell lines, RD and RH-30, with butyrate, a non-toxic anti-proliferative drug, that increased the levels of these cdkIs and resulted in the inhibition of cell growth. The authors suggest that “ the two genes are potential novel therapeutic targets for rhabdomyosarcomas”.

Detection of circulating neoplastic cells in the blood of lung neuroendocrine carcinoma patients

Begueret and colleagues describe in this issue a novel semi-quantitative reverse transcriptase –polymerase chain reaction and Southern Blotting analysis that has both diagnostic and prognostic value. They analysed chromogranin mRNA transcripts in total blood samples from 36 patients (23 with small cell lung carcinoma (SCLC), 5 with neuroendocrine lung large cell carcinoma (LCC) and 8 with typical carcinoid tumours (TC)). The test was specific and could detect 10 cancer cells/ml of blood. There were no detectable transcripts in the controls or the TC samples. In contrast, 52% of the SCLC and 80% of the LCC cases were positive. Positivity was associated with an approximately 3-fold poorer prognosis and the authors propose that this assay should be compared (in a larger cohort of patients) for its clinical usefulness with a recent immunoradiometric method that could detect chromogranin in serum.

No improvement in DFS and OS following adjuvant endocrine treatment in early endometrial cancer

As endometrial cancer is a hormone-dependent disease then adjuvant hormonal treatment may be useful. Kaufmann and colleagues report on data from a trial in 1983-9 where they randomised 388 patients with stage I/II endometrial cancer to receive tamoxifen (n=121) (30mg/day), medroxyprogesterone acetate (MPA) (n=133) (500mg/day orally) or to observation (n=134). All patients had undergone surgery consisting of abdominal hysterectomy, bilateral salpingo-oophorectomy and partial colpectomy. Adjuvant treatment was continued for 2 years or until disease progression. DFS and OS were the main endpoints. There was no difference in DFS and OS between the groups, although the side-effects were more severe following MPA treatment. There were some differences in the subgroups in these parameters ie in those with stage II disease OS was prolonged for patients treated with tamoxifen. However, these analyses included small numbers of patients. The authors concluded that the trial “failed to reveal a survival benefit for adjuvant MPA and tamoxifen in patients with early stage endometrial carcinoma”.

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