Zajicek G
H.H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Anticancer Res. 1999 Nov-Dec;19(6A):4907-12.
Despite intensive effort to cure breast cancer, treatment generally fails, as evidenced by the age adjusted mortality from breast cancer. For 60 years, breast cancer mortality remained virtually constant. As treatment failed to improve the life prospect of the average patient, it is based on false premises, e.g., Halsted's hypothesis, according to which the tumor is the only threat to the patient. Yet there is more to cancer than just the tumor. Two hallmarks of cancer, cachexia, and paraneoplasia, are usually ignored, since it is assumed that they are caused by the tumor. But, what if it is the other way around, and cancer is first of all a cachexia accompanied by a tumor? At least this could explain why in most cancers treatment fails. Cancer is a chronic systemic disease with local manifestations. Like arteriosclerosis, that is also systemic and manifested solely by its local manifestations, e.g., stroke and myocardial infarction. In the same way as treatment of an ailing heart does not cure the underlying arteriosclerosis, tumor removal does not cure cancer, since being "metabolically" systemic. It is proposed here that carcinogens deplete a vital substance and induce a metabolic deficiency that ends in cachexia. In order to survive, the organism grows a protective organ, the tumor, that replenishes the missing substance. During pre-clinical phase of cancer, deficiency is slight and compensated even by a minute tumor. With time it gets worse and the tumor has to grow more and more in order to make up for the loss, causing pain and secondary damage to vital functions. The patient seeks help and the disease starts its clinical course. When deficiency worsens, the patient becomes cachectic and dies. Such a metabolic relationship exists in pernicious anemia, that illustrates how a tumor might be protective. Cancer is viewed here as pernicious cachexia induced by the loss of a vital metabolite and compensated by the tumor. Until the discovery of the missing substance, treatment ought to preserve the tumor and alleviate its secondary manifestations.
尽管人们为治愈乳腺癌付出了巨大努力，但治疗通常还是失败了，乳腺癌的年龄调整死亡率就证明了这一点。60年来，乳腺癌死亡率几乎一直保持不变。由于治疗未能改善普通患者的生命前景，所以其基于一些错误的前提，比如霍尔斯特德假说，该假说认为肿瘤是对患者的唯一威胁。然而，癌症远不止肿瘤这么简单。癌症的两个特征，恶病质和副肿瘤综合征，通常被忽视了，因为人们认为它们是由肿瘤引起的。但是，如果事实正好相反，即癌症首先是一种伴有肿瘤的恶病质呢？至少这可以解释为什么大多数癌症治疗都会失败。癌症是一种具有局部表现的慢性全身性疾病。就像动脉粥样硬化一样，它也是全身性的，仅通过其局部表现如中风和心肌梗死来体现。就如同治疗患病的心脏并不能治愈潜在的动脉粥样硬化一样，切除肿瘤也无法治愈癌症，因为癌症是“代谢性”全身性疾病。本文提出，致癌物会耗尽一种重要物质并引发代谢缺陷，最终导致恶病质。为了生存，机体生长出一个保护性器官，即肿瘤，它可以补充缺失的物质。在癌症的临床前期阶段，缺陷很轻微，即使是微小的肿瘤也能进行补偿。随着时间的推移，情况会变得更糟，肿瘤必须不断生长以弥补损失，从而导致疼痛并对重要功能造成继发性损害。患者寻求帮助，疾病开始其临床进程。当缺陷恶化时，患者会出现恶病质并死亡。恶性贫血中就存在这样一种代谢关系，它说明了肿瘤可能是如何具有保护作用的。在这里，癌症被视为因重要代谢物缺失而引发的恶性恶病质，并由肿瘤进行补偿。在发现缺失的物质之前，治疗应该保留肿瘤并减轻其继发性表现。
