S. Guichard et al., CPT-11 converting carboxylesterase and topoisomerase I activities in tumour and normal colon and liver tissues, BR J CANC, 80(3-4), 1999, pp. 364-370
CPT-11 is a prodrug activated by carboxylesterases to the active metabolite
SN-38 which is a potent inhibitor of topoisomerase I. CPT-II is of clinica
l interest in the treatment of colorectal cancer. We evaluated the activiti
es of CPT-11 converting carboxylesterase (CPT-CE) and topoisomerase I (topo
I) in 53 colorectal tumours, in eight liver metastases and in normal tissu
e adjacent to the tumours. Both: CPT-CE and topo I activities were widely v
ariable in the malignant and the normal tissue of patients with colorectal
carcinomas. CPI-CE was only two to threefold lower in primary tumours compa
red to normal liver, suggesting that a local conversion to SN-38 might occu
r in tumour cells. CPT-CE was similar in liver and in normal colon tissues.
Levels of topo I in tumour ranged from 580 to 84 900 U mg protein(-1) and
was above 40 000 U mg protein(-1) in 11 of 53 patients. Similarly, a very h
igh ratio (> 5) between tumour and normal tissues were observed in 12 of 53
patients. An inverse correlation was observed between the topo I activity
and the clinical stage of disease. Clinical studies are in progress in our
institution to explore a possible relationship between CPT-CE and topo I ac
tivities in tumour cells and the response to CPT-11-based chemotherapy in p
atients with colorectal cancer.