Game of Clones: Battles in the Field of Carcinogenesis

Authors

Zahraa Rahal
Ansam Sinjab
Ignacio I Wistuba
Humam Kadara

Publication Date

9-1-2022

Abstract

Recent advances in bulk sequencing approaches as well as genomic decoding at the single-cell level have revealed surprisingly high somatic mutational burdens in normal tissues, as well as increased our understanding of the landscape of "field cancerization", that is, molecular and immune alterations in mutagen-exposed normal-appearing tissues that recapitulated those present in tumors. Charting the somatic mutational landscapes in normal tissues can have strong implications on our understanding of how tumors arise from mutagenized epithelium. Making sense of those mutations to understand the progression along the pathologic continuum of normal epithelia, preneoplasias, up to malignant tissues will help pave way for identification of ideal targets that can guide new strategies for preventing or eliminating cancers at their earliest stages of development. In this review, we will provide a brief history of field cancerization and its implications on understanding early stages of cancer pathogenesis and deviation from the pathologically "normal" state. The review will provide an overview of how mutations accumulating in normal tissues can lead to a patchwork of mutated cell clones that compete while maintaining an overall state of functional homeostasis. The review also explores the role of clonal competition in directing the fate of normal tissues and summarizes multiple mechanisms elicited in this phenomenon and which have been linked to cancer development. Finally, we highlight the importance of understanding mutations in normal tissues, as well as clonal competition dynamics (in both the epithelium and the microenvironment) and their significance in exploring new approaches to combatting cancer.

Keywords

Carcinogenesis, Clone Cells, Epithelium, Humans, Mutation, Neoplasms, Tumor Microenvironment, Clonal competition; Field cancerization; Field carcinogenesis; Somatic mutations; cancer evolution

DOI

10.1016/j.pharmthera.2022.108251

PMID

35850404

PMCID

PMC10249058

PubMedCentral® Posted Date

9-1-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes