Parris George E
Med Hypotheses. 2005;65(5):846-50. doi: 10.1016/j.mehy.2005.05.036.
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.
遵循杜斯伯格和拉斯尼克（《细胞运动与细胞骨架》，2000年；47卷：81 - 107页）提出的癌症是一种独立生物体物种的观点，本文探讨了作为寄生虫的癌症生态学。癌症最重要的生态特征是其进化能力。文中考虑了癌症进化的突变假说和“不稳定基因组”假说，但目前这两种假说都被认为无法充分解释癌症如何成功进化。特别是，仅靠这两种过程中的任何一种，在形成具有临床意义的肿瘤之前，细胞系就应该灭绝。此外，“不稳定基因组”一词可能应被“易变基因组”所取代，因为如果克隆要扩大，癌症基因组必须足够稳定，以便历经多代自我复制。不可检测的肿瘤发展为具有临床意义的癌症的有效进化过程中的关键步骤，据推测是来自不同细胞（例如正常细胞和异常细胞）的染色体进行类似有性生殖的重排。这种类似有性生殖的过程始于细胞融合形成多核体，多核体可能是稳定的（产生许多肿瘤中可见的多核巨细胞），或者可能经历“有丝分裂灾难”以产生多倍体细胞。多倍体细胞的细胞核可能经历一个称为“新细胞生成”的过程，在此过程中它们形成芽体并进行核分裂，随后进行胞质分裂，产生核质体（细胞质很少的小细胞），这些核质体形成新的癌症克隆系。尽管突变和不稳定（非整倍体）基因组在癌症进化中都被视为死胡同（即仅使用这些基因组修饰模式，癌症在灭绝之前不太可能发展到具有临床意义），但它们各自都会产生短暂的遗传物质，这些遗传物质可以通过细胞融合整合到具有侵袭性（即生态适应性强）表型的稳定基因组中。有人提出，在进行经典化疗的同时抑制细胞融合（或这个类似有性生殖过程中的其他步骤）可能会阻止克隆的进化和癌症的复发。同样，积极抑制病毒或其他催化细胞融合的条件也应减缓癌症克隆的进化。
