The Underexplored Links Between Cancer and the Internal Body Climate: Implications for Cancer Prevention and Treatment

In order to effectively manage and cure cancer we should move beyond the general view of cancer as a random process of genetic alterations leading to uncontrolled cell proliferation or simply a predictable evolutionary process involving selection for traits that increase cell fitness. In our view, cancer is a systemic disease that involves multiple interactions not only among cells within tumors or between tumors and surrounding tissues but also with the entire organism and its internal "milieu". We define the internal body climate as an resulting from spatial and temporal interactions among internal components themselves and with the external environment. The body climate itself can either prevent, promote or support cancer initiation and progression (top-down effect; i.e., body climate-induced effects on cancer), as well as be perturbed by cancer (bottom-up effect; i.e., cancer-induced body climate changes) to further favor cancer progression and spread. This positive feedback loop can move the system towards a "cancerized" organism and ultimately results in its demise. In our view, cancer not only affects the entire system; it is . This model provides an integrated framework to study all aspects of cancer as a systemic disease, and also highlights unexplored links that can be altered to both body climate changes that favor cancer initiation, progression and dissemination as well as or the body internal climate to hinder the success of cancer inception, progression and metastasis or improve therapy outcomes. To do so, we need to (i) identify cancer-relevant factors that affect specific climate components, (ii) develop '', (iii) define '', and (iv) develop strategies to prevent climate changes, stop or slow the changes, or even revert the changes (climate restoration).