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.

Keywords::

• genomics
• holistic
• intratumor heterogeneity
• molecular classification
• molecular pathological epidemiology
• MPE
• neoplasia
• phenome
• systems biology
• tumor–host interaction
• unique tumor paradigm

Financial & competing interests disclosure

This work was supported by US NIH grants (S Ogino received support from R01 CA151993, CS Fuchs received support from P50 CA127003, R01 CA118553 and R01 CA124908, SE Hankinson received support from P01 CA87969 and WC Willett received support from P01 CA55075). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or NIH. Funding agencies did not have any role in the decision to submit the manuscript for publication, or the writing of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.