Cancer is not a guest

Maccio, Antonio;Madeddu, Clelia

2025-01-01

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Abstract

In a recent article titled "Embracing Cancer Complexity: Hallmarks of Systemic Disease" published in Cell, Swaton et al. propose the idea of cancer as a guest that develops within a host. They discuss the possible causes and events of neoplastic cell dysregulations within an organism, highlighting events such as cachexia and thrombosis. However, we believe that to understand cancer-associated phenomena better, cancer cannot be considered a guest. In reality, cancer is born, develops, and spreads within its environment. It does not come from outside but instead uses the same system in which it lives to promote its death plan. Indeed, today we know that cancer not only causes local symptoms in the affected organ but also leads to systemic symptoms, which are evidence of inflammation associated with cancer. Inflammation is vital in controlling oncogenesis and neoplastic proliferation during the resistance phase, which is a critical moment for the immune system to demonstrate its effectiveness. However, if the immune system causes immunopathological damage, it may lead to necrosis and eventually to the tolerance phase, which can result in systemic symptoms. Understanding these phenomena thoroughly explains thrombophilia, anemia, sarcopenia, and iron metabolism disruption in advanced-stage neoplastic patients. The concept of the microenvironment takes on a different meaning in this context. The same cells that should oppose cancer in the tolerance phase now participate in a process that self-maintains, favoring the growth of the cancer and its death plan. The exact knowledge of these mechanisms is a more modern translational approach to treating cancer and its related symptoms.