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Signal Transduction and Apoptosis Pathways as Therapeutic Targets

2004; Springer Science+Business Media; Linguagem: Inglês

10.1007/978-3-540-74264-7_15

2197-8484

Pilar F. Valerón, Salvador Aznar Benitah, Juan Carlos Lacal,

Protein Kinase Regulation and GTPase Signaling

The knowledge of the cellular events that take place during the development of a disease is crucial for establishing effective therapies. During the last three decades, the design of antitumoral agents has been primarily based on the fact that tumor cells exhibit a higher proliferation rate than “normal” cells. As a consequence, drugs that are cytotoxic either by affecting DNA replication, cellular morphological integrity, or cellular metabolism, such as alkylating, antimetabolites and microtubule-destabilizing agents, have been approved as valid antitumoral therapies. Although these compounds are still used nowadays as the principal weapons against tumor development and progression, many types of tumors of epithelial origin (the main kind of solid tumors in humans) are resistant to these conventional drugs. In addition, most of these therapies have considerable side effects as a consequence of non-specific cytotoxic effects on normal non-tumorigenic cells that usually exhibit a high proliferation rate, such as the intestinal epithelium or the bone marrow. A second serious clinical issue is the acquired resistance shown by many advanced tumors towards conventional chemotherapeutics that ultimately renders the therapeutic strategy useless.