Tumor heterogeneity: does it matter?

Abstract

Introduction: It has long been recognised that tumours are composed of a mosaic of cells and numerous methods have been developed to detect tumour heterogeneity, including in situ hybridisation, multi-regional sampling, cytological assays, and whole genome and single cell sequencing. Using these methods, heterogeneity has been observed at the genetic, epigenetic, and phenotypic level in numerous cancers. With the advent of deep sequencing technology, we now appreciate a greater complexity of distinct genotypes and phenotypes that drive the biological behaviour of cancer. Despite decades of progress in detecting tumour heterogeneity, the question remains: to what extent does it matter?Areas covered: This review explores the evidence for and against the importance of tumour heterogeneity in three main areas: prognostication, development of targeted therapeutics and tumour resistance; summarising current understanding before evaluating ongoing experimental and clinical developments.Expert opinion: Theoretical understanding and in vitro detection of intratumour heterogeneity promises much but is yet to translate into meaningful clinical benefit. However, the recent emergence of a host of technological innovations and upcoming clinical trials may soon change the landscape of this field.

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

“…Recent work has revealed a great variability of the EMT program with complete and incomplete forms (see Section 3) the specific forming of which depends on tissue context and stage of tumor progression [5]. Numerous methods have been developed to detect tumor heterogeneity at the genetic, epigenetic, and phenotypic level [6]. These include multi-regional sampling (single biopsies or fine needle aspirates), cytological assays, immunohistochemistry, in situ hybridization, and omic-based technologies, i.e., whole genome and next-generation sequencing as well as single cell sequencing.…”

“…These include multi-regional sampling (single biopsies or fine needle aspirates), cytological assays, immunohistochemistry, in situ hybridization, and omic-based technologies, i.e., whole genome and next-generation sequencing as well as single cell sequencing. Liquid biopsies based on cell-free circulating tumor DNA carrying tumor-specific genetic or epigenetic alterations, and CTCs provide a new approach to circumvent the challenges of spatial heterogeneity [6]. A novel method, termed MAPit-patch, uses multiplex amplification of targeted sequences from genomic DNA followed by next-generation bisulfite sequencing.…”

Progress and applications of mass cytometry in sketching immune landscapes

“…Cell heterogeneities pose challenges for treatment selection. 177 However, this heterogeneity is often obscured in conventional screening methods that yield average measurements of bulk populations, motivating the need for a high-throughput single-cell technique. CyTOF facilitates the screening of signaling network and dynamics of baseline or stimulated status.…”

“…We expect CyTOF to be established in pharmacological research and function as a powerful drug screening tool. Cell heterogeneities pose challenges for treatment selection 177 . However, this heterogeneity is often obscured in conventional screening methods that yield average measurements of bulk populations, motivating the need for a high‐throughput single‐cell technique.…”

Circadian Genes as Therapeutic Targets in Pancreatic Cancer

“…Tumor heterogeneity is associated, in part, to the presence of CSCs (88). CSCs are a distinct proportion of the cancer cells present in the tumor, characterized by their tumorigenesis, differentiation and self-renewal capacities, but also by a slow cell cycle and an increase of ABC transporters which allow them to evade cancer therapies (89).…”