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........ published in NEWSLETTER # 50

CANCER THERAPY: DIFFERNTIATION, IMMUNOMODULATION AND ANGIOGENESIS
by Professor N. D'Alessandro, Institute of Pharmacology, Universita' degli Studi, Palermo (Italy)

The insufficient selectivity of antitumor drugs currently available and the frequent phenomenon of drug resistance represent a major obstacle to further advances in cancer treatment. With this in mind, the aim of the NATO ASI held from 17 to 27 October 1992 in Erice, of which this book (NATO ASI SERIES H75) contains the proceedings, was to examine comprehensively the basic and clinical conditions of some innovative approaches which may support or even substitute chemotherapy.

A general consensus stated that cancer cells are characterized by being arrested at an immature level of development while retaining their proliferative capacity; a rational approach thus involves the induction of tumor cell differentiation to a mature stage, where proliferation ceases. In this respect, several possible therapeutic options are discussed. For example, the resources of interferons or of selected doses and mechanisms of conventional antineoplastic agents. It is also shown how all_trans retinoic acid induced a very high rate of complete remissions in acute promyelocytic leukemia. This represents a solid model of differentiation therapy in human malignancies.

Modulation by biological agents, cytotoxic effector cells and drugs is considered in its attempt to boost endogenous antitumor defenses and/or to render neoplastic cells more susceptible to the host attack. Many cases of useful interaction between anticancer drugs and immunity are underlined, including chemical xenogenization and the reversal of drug resistance by biological factors. The use of IL_2 in advanced cancer is reviewed; emphasis is also placed on the possibility of improving the diagnostic and therapeutic efficacy of monoclonal antibodies through the use of interferons, which can enhance the expression of human tumor antigens.

In the last section, the important aspect of interfering with tumor vessel development and function, and with the consequent metastatic potential, is taken into account. There are complete reports on the biology of the process, its factors and genes. The tools of antiangiogenesis, possibly including suramin, are surveyed, and the best strategy for their clinical use discussed. In summary, the readers of this book are exposed to new concepts and/or models to be considered or applied in their laboratories or clinical practice. Indeed, there is evidence that the exploitation of discrete mechanisms in differentiation, immunomodulation or angiogenesis may be of therapeutic value, at least in selected human neoplasms. This situation could well improve in the next few years and represent a fertile area for further NATO activities.
Reference books: A53, A159, A209, A232, H52, H56. H66, H75, H76

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