Retinoids: Their Physiological Function and Therapeutic Potential
Retinoids have received considerable attention in recent years and due cognizance has been given to their versatility as biological response modifiers, as evidenced by the virtually explosive growth of literature in this field in the past few years. This volume has been designed to give a current state-of-the-art picture of retinoids. The perceived potential of retinoids in the treatment of certain disease stated has initiated attempts at identifying and synthesizing new retinoid derivatives with definable and selective effects on aberrant biological phenomena. Appropriately, therefore, we begin with the chemistry of retinoids and their derivatives together with discussions of their biological activity. Major advances have been made in understanding the mechanisms by which retinoids modulate physiological and phenotypic traits of cells. The transduction of retinoid signaling by the mediation of nuclear receptors of the steroid/thyroid receptor superfamily has now been studied extensively and the cloning and defining the characteristics of these receptors has been a focus of discussion in this volume. Retinoids also markedly modulate the transduction of extracellular signals such as those imparted by growth factors and hormones, and thus actively influence and control cellular proliferative patterns. Retinoids can alter epidermal growth factor receptor expression (Kawaguchi et al., 1994), responsiveness to thyroid hormone (Esfandiari et al., 1994; Pallet et al., 1994), inhibit the proliferative responses of hematopoietic progenitor cells to granulocyte colony stimulating factor (Smeland et al., 1994), and modulate secretion on interleukins by leukaemic cells (Balitrand et al., 1994), among other things. This has obvious implications for pharmacological manipulation of deregulated growth (Dickens and Colletta, 1993; Mulshine et al., 1993). Apoptosis is another component in the regulation of growth control. Apoptotic cell death is influenced by several agents and retinoids may function by interfering with apoptotic pathways of regulation of growth control and quite legitimately, therefore, the importance of this aspect of retinoid function has been duly recognized here.