How many molecular subtypes? Implications of the unique tumor principle in personalized medicine

Abstract

Cancers are complex multifactorial diseases. For centuries, conventional organ-based classification system (i.e., breast cancer, lung cancer, colon cancer, colorectal cancer, prostate cancer, lymphoma, leukemia, and so on) has been utilized. Recently, molecular diagnostics has become an essential component in clinical decision-making. However, tumor evolution and behavior cannot accurately be predicted, despite numerous research studies reporting promising tumor biomarkers. To advance molecular diagnostics, a better understanding of intratumor and intertumor heterogeneity is essential. Tumor cells interact with the extracellular matrix and host non-neoplastic cells in the tumor microenvironment, which is influenced by genomic variation, hormones, and dietary, lifestyle and environmental exposures, implicated by molecular pathological epidemiology. Essentially, each tumor possesses its own unique characteristics in terms of molecular make-up, tumor microenvironment and interactomes within and between neoplastic and host cells. Starting from the unique tumor concept and paradigm, we can better classify tumors by molecular methods, and move closer toward personalized cancer medicine and prevention.

Figure 1. A variety of endogenous and exogenous factors contribute to a diversity of tumor–host interactions and carcinogenesis processes, leading to intertumor heterogeneity and the uniqueness of each tumor

To simplify, only several examples of such factors are shown, and no interaction between the factors is depicted. In addition, there is probably a chance factor in the process of carcinogenesis.

Figure 2. Tumorigenesis pathways

Each tumor pathway is unique, but we can classify similar tumor pathways into one type or one subtype. See explanation in the section titled ‘How many tumor subtypes?’