Aberrant Expression and Function of Retinoid Receptors in Cancer

Retinoids are a group of structural and functional analogs of vitamin A. They regulate a number of fundamental physiological processes including vision, reproduction, metabolism, differentiation, bone development, and pattern formation during embryogenesis (De Luca 1991; Gudas et al. 1994; Lotan 1995a). Certain retinoids are capable of modulating cell growth, differentiation, and apoptosis and suppressing carcinogenesis in a variety of tissue types (e.g., lung, skin, mammary gland, prostate, bladder) in animal models (Moon et al. 1994; Lotan 1996) and in clinical trials with patients with premalignant or malignant lesions of the oral cavity, cervix, bronchial epithelium, skin, and other organs (Kraemer et al. 1992; Hong and Itri 1994; Lotan 1996; Hong and Sporn 1997; Moon et al. 1997). Some retinoids exhibit antitumor activity against fully malignant cells in vitro as reflected by suppression of proliferation and induction of differentiation or apoptosis (Amos and Lotan 1991; Lotan et al. 1991; Gudas et al. 1994; Lotan 1995a). Consequently, retinoids are considered as potential therapeutic agents as well (Smith et al. 1992). The ability of all-trans-retinoic acid (ATRA) to induce differentiation of acute promyelocytic leukemia cells into granulocytes is the basis for its therapeutic activity in patients and ATRA is currently used for therapy of this type of cancer (Degos 1997; Suooignet et al. 1997; Tallman et al. 1997; see Chap. 11, Sect. III).