General prognostic indicators of cancer : emphasis on serum alkaline DNase activity

Abstract

Evaluation de l’efficacité des thérapeutiques anticancéreuses et détection précoce des récidives tumorales par la mesure de l’activité de la DNase alcaline dans le sérum : étude clinique et expérimentale. Une étude clinique menée au sein de différents hôpitaux belges et à laquelle ont collaboré des centres français et suédois a permis d’analyser chez 800 sujets sains et chez 600 patients atteints de différents types de cancers les variations d’activité de la DNase alcaline sérique grâce à la technique qui a été mise au point au laboratoire. Cette étude montre l’intérêt clinique que représentent les variations d’activité sérique de cet enzyme en apportant des informations dans le cadre du suivi thérapeutique et dans le cadre de la détection précoce des récidives. Les mêmes types de variations d’activité de la DNase ont été observées chez le rat au cour du développement et après traitement de tumeurs transplantables. toutes variations observées d’une part, chez les patients cancéreux pendant leur suivi thérapeutique et d’autre part, chez les rats, semblent indiquer que l’activité de la DNase alcaline sérique est étroitement influencée par la présence et l’évolution de la tumeur dans l’organisme. Les résultats de ces recherches ont fait l’objet de neuf publications dans des revues internationalesThat certain neoplasms may exist in the organism during many years without expressing clinically detectable signs of malignancy is well know to clinicians (Rustin, 1980 ; Winters, 1983 ; Cohen and Diamond, 1986). It is now generally accepted that early detection of certain cancers significantly increases the survival rate, mostly because surgery is possible at that stage (Woodruff, 1980). Although some progress has been made, still in most cases the clinical detection of cancer occurs when the patient is symptomatic, i.e. when tumor mass has reached a certain size, and often has developed metastasis (Woodruff, 1980; Cohen and Diamond, 1968) That certain substances are specifically produced by the tumor cells, and released to the circulation in detectable amounts has been recognized for many years (Rustin, 1987). In the 1930”s Guttman and colleagues introduced the concept of tumor markers by observing that elevation in serum acid phsophatase activity correlated with advanced carcinoma of the prostate. But only during the mid-1960”s, the current interest in tumor markers arose with the discovery of substances called oncofoetal proteins. Since then, there has been a rapid development in new biological and biochemical markers of neoplasia to diagnose, identify and localize both malignant and premalignant lesions. These tumor-associated substances include antigens, enzymes, and hormones, most of which are specific for only one or a few types of tumors (Chu et al., 1982). From a clinical point of view, applications of tumor markers should include early tumor detection and diagnosis but also therapeutic monitoring (i.e., predicting rapidly the effect of therapy and detecting recurrent and/or occult cancer) but, most currently available tumor markers to not cover all these aspects. In facts, there are only a few tumor markers that have a well proved place in clinical decision making: human chorionic gonadotrophin (HCG) in trophoblastic tumors; alpha fetoprotein (AFP) and HCG in germ-cell tumors and monoclonal immunoglobulins detectable by serum electrophoresis (M proteins) in myeloma (Pohl et al., 1983; Borek, 1984; Rustin, 1987). However, the failure of these markers to detect a broad spectrum of malignant diseases and the number of false positive observations restrict their usefulness as general prognostic indicators for the surveillance of presence, regression or progression of many tumor types (Economidou-Karaoglou and Lans, 1989). In particular, the need for tests that rapidly predict the sensitivity of the tumor to therapy and maintenance of remission, or detect an eventual occult disease for a wide variety of tumors, has become a challenging problem for the clinician. Indeed, “General Prognostic Indicators” might permit a rapid selection of more effective therapies and a better monitoring of cancer patients. The aims of the present work are: a) to review the present state of the art with regard to compounds and enzyme activities present in serum that are or might be used as such tests; b) to report and discuss both clinical and experimental evidences supporting the hypothesis that serum alkaline DNase is a new biochemical marker which has the quality of a “General Prognstic Indicator” of cancerThèse d'agrégation de l'enseignement supérieur (Faculté de médecine) -- UCL, 199