ImmunoMet Oncogenesis: A New Concept to Understand the Molecular Drivers of Cancer

Cancer progression unfolds as a complex multistep process involving genetic, epigenetic, mutational, inflammatory, and metabolic disruptions to key signaling pathways within affected organs. The cumulative effect of these disturbances determines the cellular growth properties and governs the trajectory toward malignancy. The severity and interplay of these disruptions are pivotal in dictating whether the pathological changes escalate into advanced malignancy. Increasingly, researchers are uncovering the molecular mechanisms underlying abnormal inflammation and metabolism, many of which are recognized as prominent contributors during pre-cancerous conditions. These mechanisms are now acknowledged as significant drivers of the malignant phenotype, emphasizing their role in cancer development.

Recent advances have introduced a promising approach to utilizing signaling pathways linked to inflammation and metabolism as cancer biomarkers. These biomarkers extend beyond the traditionally characterized pathways associated with metabolic dysfunction or inflammatory processes. By focusing on emerging elements that influence proliferation, inflammation, and metabolism, it is becoming possible to identify key factors driving the cancer phenotype. Among these elements, AMPK and leptin serve as regulators of metabolism, while NOD2/RIPK2 and TAK1 are integral to inflammatory responses. Lactate and pyruvate transporters, collectively known as monocarboxylate transporters (MCTs), are linked to mitochondrial biogenesis and metabolic activity. Additionally, RASSF1A plays a versatile role, influencing proliferation, cell death, cell cycle regulation, inflammation, and epigenetic modifications.

This review introduces the concept of “ImmunoMET Oncogenesis,” a tripartite framework encompassing proliferation, inflammation, and metabolism as fundamental drivers of carcinogenesis. The term highlights the need to integrate an understanding of these interconnected pathways to fully elucidate the dynamics of cancer progression. Proliferation, as a hallmark of malignant transformation, involves dysregulated cellular growth mechanisms. Inflammation contributes through chronic immune activation and tissue disruption, while metabolic alterations fuel the energy demands of rapidly growing cancer cells. Together, these factors interact with classical drivers of malignancy, ultimately shaping the cancerous state.

The proposed ImmunoMET Oncogenesis framework emphasizes that a comprehensive understanding of cancer requires dissecting how these signaling pathways are altered and how their disruptions influence disease progression. VB124 This integrated perspective provides a basis for identifying novel therapeutic targets and strategies, enhancing our ability to mitigate the impacts of proliferation, inflammation, and metabolic abnormalities in driving cancer. By recognizing the intricate interplay of these processes, ImmunoMET Oncogenesis sets the stage for advancing both our theoretical understanding and clinical approach to combating malignancy.