Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications

Abstract

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.

From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies

“…With such a number of randomly distributed mutations, the distribution of these mutations along the genome is unique in each particular cell of 10 9 different cancer cells. All of the cells are different from all others in this particular tumor, and as so in all other tumors in the world [14][15][16]29,30].…”

“…Since then, quite a number of reports have confirmed the points of view expressed there. For the most recent reviews, see, for example, [15][16][17]. In brief, there are more than 100 distinct types of cancer in specific organs [18].…”

Multiplexed and millimeter-scale fluorescence nanoscopy of cells and tissue sections via prism-illumination and microfluidics-enhanced DNA-PAINT

“…To our knowledge, this is the first time that clinical samples have been analyzed with nanoscopic resolution with millimeter-scale FOVs. Hence, PRIME-PAINT joins the growing list of spatial omics tools [40][41][42][43] with the unique capability of analyzing nanoscopic protein localizations and interactions.…”

Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future

“…Patient-related factors including the status of the endogenous immune system, performance status, and comorbidities, as well as tumor burden and disease sites may well influence response to therapy ( 6 ). Furthermore, features of the tumor itself, including dynamic and heterogenous tumor antigen expression ( 84 ), complicates the routine assessment of antitumor activity of TIL products since practicalities of tumor procurement may limit capturing the full spectrum of antigens present in the patient ( 85 ). Thus, some tumor-specific T-cell clones present in the TIL product may be improperly designated tumor nonreactive.…”