Mechanisms and clinical implications of tumor heterogeneity and convergence on recurrent phenotypes

Abstract

Tumor heterogeneity has been identified at various -omic levels. The tumor genome, transcriptome, proteome, and phenome can vary widely across cells in patient tumors and are influenced by tumor cell interactions with heterogeneous physical conditions and cellular components of the tumor microenvironment. Here, we explore the concept that while variation exists at multiple -omic levels, changes at each of these levels converge on the same pathways and lead to convergent phenotypes in tumors that can provide common drug targets. These phenotypes include cellular growth and proliferation, sustained oncogenic signaling, and immune avoidance, among others. Tumor heterogeneity complicates treatment of patient cancers as it leads to varied response to therapies. Identification of convergent cellular phenotypes arising in patient cancers and targeted therapies that reverse them has the potential to transform the way clinicians treat these cancers and to improve patient outcome.

Neural crest delamination and migration: Looking forward to the next 150 years

“…Depending on the tools one uses, heterogeneity can be found at multiple levels (genetic, genomic, proteomic, cell size, shape and behavior, topology). Cellular heterogeneity is one of the main driving force of cancer progression (McQuerry, Chang, Bowtell, Cohen, & Bild, ). In normal tissue, heterogeneity was originally proposed as a way to maximize cell populations’ responses to environmental changes to ensure adaptability and robustness.…”

“…Depending on the tools one uses, heterogeneity can be found at multiple levels (genetic, genomic, proteomic, cell size, shape and behavior, topology). Cellular heterogeneity is one of the main driving force of cancer progression (McQuerry, Chang, Bowtell, Cohen, & Bild, 2017).…”

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

“…Tumors are perceived as composite systems that diversify at the molecular, cellular, and architectural levels, accounting for phenotypic and functional heterogeneity ( 1 ). With divergence at the genetic, epigenetic, transcriptomic, proteomic, and cellular levels tumor heterogeneity is regarded as an essential barrier hindering the development of curative anti-cancer therapies ( 2 ). In this perspective, giant multinucleated or large nucleated cells denoted as polyploid giant cancer cells (PGCC) appear to significantly contribute to the shaping and the composition of cancer genomes and tumor evolution, rendering them crucial therapeutic targets to fight therapy resistance ( 3 ).…”

The Challenge of Evaluating Response to Peptide Receptor Radionuclide Therapy in Gastroenteropancreatic Neuroendocrine Tumors: The Present and the Future.

“…However, tumors are typically characterized based on a single biopsy specimen, which bears the inherent risk of an underestimation of the tumor grade [34]. It is known that tumor heterogeneity is subject to space (intertumoral and intratumoral heterogeneity) and time (more aggressive cell clones developing over time) [35,36]. Thus, grading heterogeneity between primary and secondary lesions is not negligible.…”