Genetic chaos and antichaos in human cancers George Adrian Calin, 1 Catalin Vasilescu, 2 Massimo Negrini, 1,3 Giuseppe Barbanti-Brodano 3 1 Thomas Jefferson University, Philadelphia, USA; 2 Fundeni Hospital, Bucharest, Romania; 3 University of Ferrara, Ferrara, Italy Summary Cancer is considered the genetic disease with the most complex pathogenetic mechanism. Contrary to normal human tissues, which function in a highly ordered and uniform manner, tumor tissues were considered to develop chaos. Here we propose that analysis of human neoplasia according to the concepts of chaos and antichaos allowed to distinguish two main types of cancers: the hematopoietic cancers, characterized by the orderly antichaos and solid cancers governed by a disordered complex of genetic and molecular events characteristic of a chaotic pattern. Genetic chaos and antichaos have generated rules that can be applied to the diagnosis and therapy of human tumors. ª 2003 Elsevier Science Ltd. All rights reserved. INTRODUCTION Chaos theory is a new form of analysis to study complex biological systems Chaos is associated with the discipline of nonlinear dy- namics, which deals with the study of systems that re- spond to stimuli in a disproportionate way. Chaos is in fact a misnomer, because the ‘deterministic chaos’ is not the same as chaos in the literary sense of complete dis- organization or randomness (1). The easier way to un- derstand this entity is to compare it to two other situations with which we are more familiar: random behavior and periodic behavior. Random behavior is never repetitive and is inherently unpredictable, while periodic behavior is highly predictable because it is al- ways repeated at finite time intervals. Although chaotic behavior, like random behavior, looks disorganized, it is really deterministic (2). With other words, deterministic chaos means order disguised as disorder. On the con- trary, the orderly structures governed by mechanisms acting to control chaos are defined as ‘antichaos’ (3). While chaos is characterized by heterogeneity and di- versity, antichaos is characterized by homogeneity and uniformity. Chaotic systems exhibit several distinctive features, such as sensitive dependence on initial condi- tions, meaning that very small differences in initial conditions will be amplified to large differences in be- havior at later times, and unpredictable evolution as chaotic behavior is never exactly repeated (2). Tumorigenesis is considered to be a typical deterministic chaotic process Cancer is considered the genetic disease with the most complex pathogenetic mechanism (4,5). Indeed, hun- dreds of genes have been closely correlated to cancer. Two major classes of cancer-related genes have been discovered. The first class comprises oncogenes (OG), which result from activation of proto-oncogenes and stimulate growth and proliferation of tumor cells, while the second class includes tumor suppressor genes (TSG) which control cell proliferation and, when inactivated, release their growth constraints on cells, leading to un- controlled proliferation. The existence of several other types of genes, such as predisposing genes, modifier genes, caretaker genes or landscaping genes, each with a specific involvement in the neoplasia pathways, is now a Medical Hypotheses (2003) 60(2), 258–262 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0306-9877(02)00383-3 258 Received 7 January 2002 Accepted 8 May 2002 Correspondence to: George Adrian Calin, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Bluemle Life Science Building Room 1006, Philadelphia, PA 19107, USA. Phone: 1-215-503-4655; Fax: 1-215-923-4498; E-mail: George.Calin@mail.tju.edu