Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications

Simple Summary Cancer heterogeneity, which occurs in most cancer patients, has been known and studied by experienced pathologists since the early 19th century. Intratumoral heterogeneity between cancer cells can arise from complex genetic, epigenetic, and metabolic modifications under the influence of the tumor microenvironment and confers considerable adaptability to tumors. Despite major advances in cancer therapy, tumoral heterogeneity remains a major obstacle to the successful treatment of cancer. In this review, we highlight the role of intratumoral heterogeneity, focusing on the clinical and biological implications of this phenomenon. Though heterogeneity of cancers is recognized and has been much discussed in recent years, the concept often remains overlooked in different routine examinations. Indeed, in clinical or biological articles, reviews, and textbooks, cancers and cancer cells are generally presented as evolving distinct entities rather than as an independent heterogeneous cooperative cell population with its self-oriented biology. There are, therefore, conceptual gaps which can mislead the interpretations/diagnostic and therapeutic approaches. In this short review, we wish to summarize and discuss various aspects of this dynamic evolving heterogeneity and its biological, pathological, clinical, diagnostic, and therapeutic implications, using thyroid carcinoma as an illustrative example.