Vnitr Lek 2001, 47(8):510-515

[Perspectives of medical therapy of solid tumours].

I Koza: Interna klinika, Národný onkologický ústav, Bratislava.

In the course of 55 years of its existence clinical chemotherapy succeeded in curing some types of leukaemia, aggressive lymphomas and some patients with some solid tumours. Other patients with solid tumours, due to treatment with cytostatics, hormones and immunomodulators, survive longer and have a better quality of life. Further improvement of results of medical treatment of solid tumours may be foreseen from new classical cytostatics, hormones and immunomodulators and better use of known cytostatics. Liposomal forms of cytostatics are at least equally effective and less toxic than original classical cytostatics. Pegylated forms of cytostatics are more suitable for patients and and will be probably more effective than non-pegylated foms. Rational approaches to treatmet inhibiting angiogenesis and transduction of signals in tumour cells reduce the proliferation of tumour cells and achieve remission of the neoplastic disease. Inhibition of cytoplasmic tyrosine kinases and tyrosine kinases of growth factor receptors reduces also the proliferation activity of tumour cells and some clinical studies provide evidence of their effectiveness in the treatment of human tumours. Inhibitors of cycline dependent kinases stop the movement of tumour cells across some stages of the cellular cycle and thus inhibit their proliferation. Inhibitors of pharanesyl transferase prevent the activation of ras oncogenes, the formation of pharnesyl isoprenoid and its incorporation into Rh0 proteins, interfere with actin regulation, adhesion and proliferation of cells. These new drugs are less toxic than cytostatics and have a cytostatic as well as cytocidal effect. Their effectiveness is manifested by stabilization or slight regression of the tumour. To achieve an effect long-term treatment with an optimal dose is necessary which is not necessarily identical with the maximum tolerated dose and after discontinuation of treatment a relapse occurs. Combination of new inhibitors of cell division with classical cytostatics enhances the effectiveness of treatment. In the immunotherapy of tumours monoclonal antibodies are most important which have their own antitumourous activity and increase the effectiveness of cytostatics. Vaccines, similarly as gene therapy and modulators of resistance to cytostatics have so far limited indications. Rationally prepared molecules of new substances acting on new objectives of proliferation of tumour cells have a great chance to improve the results of treatment of tumours.