The lethal symbiont: exploring the pathophysiology of cancer.

From its early genesis, cancer is integrated with the surrounding tissue. Its very existence depends on surrounding normal tissue cells engaging with cancer cells to create an alternative tissue environment. This emerging abnormal structure becomes connected with the host organism via blood, lymphatic vessels, and neural connections. Through those connections, the cancer mass communicates and perturbs the entire organism altering various aspects of the steady-state body physiology. At early, asymptomatic stages, the induced changes within distant organs that harbor the potential to facilitate the spread of cancer are termed "premetastatic niche." Many processes involved with premetastatic changes hijack processes typical in other contexts such as development, injury, or infections, but their co-occurrence creates a new alternative physiology. The cancer to body connections not only have important consequences for the efficacy of cancer therapy but also enable cancer to evolve and adapt under the very pressure of those treatments. Furthermore, as cancer-induced changes are closely related to other physiological challenges, extrinsic perturbations such as diet, injury, and other inflammatory events have a strong impact on the tumor disease. As the disease progresses, the complex intersection of inflammatory, metabolic, and regenerative changes creates an escalating cascade of events causing cancer-related syndrome, such as cachexia, that threatens the homeostasis of the entire body and can, per se, be deadly. In this article, we will review the recent advances in the understanding of cancer as a systemic malady.