La Torre F, Silpigni A, Tomasello R, Picone G S, La Torre I, Aragona M
Istituto di Clinica Oncologica e di Ricerca sui Tumori, Università degli Studi, Messina.
Minerva Med. 1998 Jun;89(6):229-39.
The paper describes the main adaptive mechanisms involved in the carcinogenic process. As a result of the action of carcinogenic agents (physical, chemical, biological), and in relation to the functional status of the affected cells, a number of systems are triggered off: detoxification and conjugation systems, the metabolisation of the said agents, DNA repairing enzymes, increased shock proteins (HSP), the induction of clonal proliferation. All these systems are valuable to the survival of the body and the species and culminate in the apoptosis of damaged cells as the last attempt at adaptation of a social kind for the good of the body. When these compensation mechanisms prove ineffective, imprecise or are exceeded by cell adaptive capacity, the resulting structural and functional alterations trigger off (induction) a very long process which often lasts between one and two thirds of the body's life, in various stages, multistep and multifactorial: this neoplastic transformation leads to a purposeless, egoistic, anarchic proliferation of cells which wish to survive at all costs, even to the detriment of the body of which they form part. Following the exhaustion of cell adaptive defences, there is an accumulation of additional genetic alterations (promotion and progression), the cells become manifestly neoplastic and continue their egoistic adaptation, according to the laws of natural selection: the cells which survive are those which adapt best to the hostile environment of the host's body, which are unaffected by proliferation control mechanisms (contact inhibition, differentiation factors, apoptosis, etc.), which make the best of the growth factors present in their microenvironment, which accomplish the so-called decathlon of the metastatization process, namely acquiring new capacities which can overcome the basal membrane, invade tissues to which they are attracted and continue to proliferate. Manifestly neoplastic cells become not self at a later stage, managing to escape the immune system using various adaptive mechanisms which induce immune tolerance/anergy. From this point of view, cancer may be regarded as an incidental factor in the host's cell adaptation processes; the latter are much more important from a biological point of view and their absence is incompatible with life: cancer might therefore be regarded as a cell adaptation pathology.
本文描述了致癌过程中涉及的主要适应性机制。由于致癌因素（物理、化学、生物）的作用，并与受影响细胞的功能状态相关，一系列系统被触发：解毒和结合系统、所述致癌因素的代谢、DNA修复酶、热休克蛋白（HSP）增加、克隆增殖的诱导。所有这些系统对机体和物种的生存都很重要，并最终导致受损细胞凋亡，这是机体为自身利益进行的最后一种社会性适应尝试。当这些补偿机制被证明无效、不准确或超出细胞适应能力时，由此产生的结构和功能改变会引发一个非常漫长的过程，这个过程通常持续机体寿命的三分之一到三分之二，分多个阶段、多步骤且多因素：这种肿瘤转化导致细胞无目的、自私、无序的增殖，这些细胞不惜一切代价想要存活，甚至损害它们所属的机体。细胞适应性防御耗尽后，会积累更多的基因改变（促进和进展），细胞明显发生肿瘤性变化，并根据自然选择规律继续其自私的适应：存活下来的细胞是那些最能适应宿主机体恶劣环境的细胞，它们不受增殖控制机制（接触抑制、分化因子、凋亡等）的影响，能充分利用微环境中存在的生长因子，完成所谓的转移过程十项全能，即获得能够突破基底膜、侵入它们被吸引的组织并继续增殖的新能力。明显发生肿瘤性变化的细胞在后期变得“非己”，利用各种诱导免疫耐受/无反应性的适应性机制设法逃避免疫系统。从这个角度来看，癌症可被视为宿主细胞适应过程中的一个偶然因素；从生物学角度来看，后者更为重要，没有它们生命将无法维持：因此癌症可被视为一种细胞适应性病理学。
