Tumor Evolutionary Principles: How Intratumor Heterogeneity Influences Cancer Treatment and Outcome.

Am Soc Clin Oncol Educ Book

From the UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, London, United Kingdom; The Francis Crick Institute, London, United Kingdom.

Published: January 2017

Recent studies have shown that intratumor heterogeneity contributes to drug resistance in advanced disease. Intratumor heterogeneity may foster the selection of a resistant subclone, sometimes detectable prior to treatment. Next-generation sequencing is enabling the phylogenetic reconstruction of a cancer's life history and has revealed different modes of cancer evolution. These studies have shown that cancer evolution is not always stochastic and has certain constraints. Consideration of cancer evolution may enable the better design of clinical trials and cancer therapeutics. In this review, we summarize the different modes of cancer evolution and how this might impact clinical outcomes. Furthermore, we will discuss several therapeutic strategies for managing emergent intratumor heterogeneity.

Download full-text PDF

Source
http://dx.doi.org/10.1200/EDBK_158930DOI Listing

Publication Analysis

Top Keywords

intratumor heterogeneity
16
cancer evolution
16
modes cancer
8
cancer
6
tumor evolutionary
4
evolutionary principles
4
intratumor
4
principles intratumor
4
heterogeneity
4
heterogeneity influences
4

Similar Publications

Liquid biopsy techniques have developed rapidly in recent years and demonstrated success in cancer detection, disease characterization, and ongoing disease monitoring. These components, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and cell-free DNA (cfDNA), offer minimally invasive diagnostic tools that provide valuable insights into the genomic landscape of tumors. Its applications have expanded to include various malignancies, including renal cell carcinoma (RCC).

View Article and Find Full Text PDF

Tumour hypoxia in driving genomic instability and tumour evolution.

Nat Rev Cancer

January 2025

Translational Oncogenomics Laboratory, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.

Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair.

View Article and Find Full Text PDF

Cell-to-cell heterogeneity in lipid signaling underlies variations in response and recurrence for many cancers, including leukemias. A highly parallel, miniaturized thin-layer chromatographic platform capable of assaying single cells was developed. Ultrasmall volumes (50 pL) of standard fluorescent lipids were separated with excellent repeatability, reproducibility, and limits of detection.

View Article and Find Full Text PDF

This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion.

View Article and Find Full Text PDF

Cancer phylogenetic inference using copy number alterations detected from DNA sequencing data.

Cancer Pathog Ther

January 2025

School of Biosciences and Medicine, University of Surrey, Guildford GU2 7XH, UK.

Cancer is an evolutionary process involving the accumulation of diverse somatic mutations and clonal evolution over time. Phylogenetic inference from samples obtained from an individual patient offers a powerful approach to unraveling the intricate evolutionary history of cancer and provides insights that can inform cancer treatment. Somatic copy number alterations (CNAs) are important in cancer evolution and are often used as markers, alone or with other somatic mutations, for phylogenetic inferences, particularly in low-coverage DNA sequencing data.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!