title: Clinically significant cancer evolves from transient mutated and/or aneuploid neoplasia by cell fusion to form unstable syncytia that give rise to ecologically viable parasite species.
abstract: Following the idea of Duesberg and Rasnick (Cell Motil Cytoskeleton 2000; 47:81-107) that cancer is a separate species of organism, the ecology of cancer as a parasite is examined. The most important ecological feature of cancer is its ability to evolve. The mutation hypothesis and the "unstable genome" hypothesis of cancer evolution are considered but neither of these current hypotheses is believed to adequately explain how cancer successfully evolves. In particular, either of these processes alone should lead to extinction of the cell line before a clinically significant neoplasm is achieved. Moreover, the term "unstable genome" probably should be replaced by "labile genome" because cancer genomes must be stable enough to reproduce themselves through many generations if the clone is to expand. The key step in productive evolution of undetectable neoplasia into clinically significant cancer is hypothesized to be sex-like resorting of chromosomes from different cells (e.g., normal and abnormal cells). The sex-like process begins with cell fusion to form a syncytium, which may be stable (producing multinucleated giant cells seen in many tumors) or which may undergo "mitotic catastrophe" to produce polyploidy cells. The nuclei of polyploid cells may undergo a process called "neosis" in which they form buds and undergo karyokinesis followed by cytokinesis to yield karyoplasts (small cells with little cytoplasm) that found new cancer clone lines. Although both mutations and unstable (aneuploid) genomes are seen as dead ends in cancer evolution (i.e., using only these modes of genome modification, cancers would not likely advance to clinical significance before becoming extinct), they each produce transient genetic material, which can be incorporated into stable genomes with aggressive (i.e., ecologically fit) phenotypes by cell fusion. It is proposed that inhibition of cell fusion (or other steps in this sex-like process) concurrent with classical chemotherapy might prevent evolution of the clones and recurrence of the cancer. Similarly, active suppression of viruses or other conditions that catalyze cell fusion should also slow down evolution of cancer clones.
authors: antimony_121@hotmail.com
authors: George E
authors: GE
authors: Parris
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000782:Aneuploidy; D000818:Animals; D005075:Biological Evolution; D002459:Cell Fusion; D049109:Cell Proliferation; D002470:Cell Survival; D015726:Giant Cells; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000469:parasitology* / Q000473:pathology / Q000503:physiopathology*