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

The appearance of cancer progresses through a multistep process that includes genetic, epigenetic, mutational, inflammatory and metabolic disturbances to signaling pathways within an organ. The combined influence of these changes will dictate the growth properties of the cells; the direction of further malignancy depends on the severity of these "disturbances". The molecular mechanisms driving abnormal inflammation and metabolism are beginning to be identified and, in some cases, are quite prominent in pre-condition states of cancer and are significant drivers of the malignant phenotype. As such, utilizing signaling pathways linked to inflammation and metabolism as biomarkers of cancer is an emerging method and includes pathways beyond those well characterized to drive metabolism or inflammation. In this review, we will discuss several emerging elements influencing proliferation, inflammation and metabolism that may play a part as drivers of the cancer phenotype. These include AMPK and leptin (linked to metabolism), NOD2/RIPK2, TAK1 (linked to inflammation), lactate and pyruvate transporters (monocarboxylate transporter [MCT], linked to mitochondrial biogenesis and metabolism) and RASSF1A (linked to proliferation, cell death, cell cycle control, inflammation and epigenetics). We speculate that the aforementioned elements are important drivers of carcinogenesis that should be collectively referenced as being involved in "ImmunoMET Oncogenesis", a new tripartite description of the role of elements in driving cancer. This term would suggest that for a better understanding of cancer, we need to understand how proliferation, inflammation and metabolic pathways are impacted and how they influence classical drivers of malignant transformation in order to drive ImmunoMET oncogenesis and the malignant state.