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Page 2 of 31 Paul J Cancer Metastasis Treat 2020;6:29 I http://dx.doi.org/10.20517/2394-4722.2020.63

Figure 1. Three levels of organization

organismic level, the networks are comprised of interactions between different body systems (endocrine,
[1-3]
nervous, immune, etc.). As described by the seminal work of Denis Noble these three levels of networks
(cellular, tissular, organismic) [Figure 1] are co-dependent and there is no priviledged level of causation.
They interact and influence each other.

Cancer is also a multi-layered disease with multiple complex networks of interactions located at different
levels, (i.e., cellular, tissular, organismic). The focus on the genome, the cancer cells, or even the cancer
tissues, is too narrow and, in order to better understand the cancer process, there is an urgent need to
zoom-out and broaden our perspective by including a broader, organismic level.

We define a system as a dynamic entity of several interacting components that are co-dependent and
function in an integrated way. A single cell, an organ, the entire human body are all systems. In the present
paper, I will focus on cancer at the macroscopic level. Macroscopically, experimental data accumulated over
more than a decade, supports the concept of a cancer system formed by several geographically separated
cancer tissues (the primary tumor, the local and the distant metastasis). The cancer system and the body
systems are co-dependent and, through their interaction, new cancer induced pathologic systemic networks
(CISPN) appear and the whole organism is “cancerized” to support cancer development [Figure 2].