Genetic and epigenetic regulation of cancer coagulome - lessons from heterogeneity of cancer cell populations.
Thromb Res
; 191 Suppl 1: S99-S105, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32736787
ABSTRACT
Cancer-associated thrombosis (CAT) is a morbid, potentially life threatening and biologically impactful paraneoplastic state. At least in part, CAT is likely driven by cancer-specific mechanisms the nature of which is still poorly understood, hampering diagnostic, prophylactic and therapeutic efforts. It is increasingly appreciated that cancer-specific drivers of CAT include a constellation of oncogenic mutations and their superimposed epigenetic states that shape the transcriptome, phenotype and secretome of cancer cell populations, including the repertoire of genes impacting the vascular and coagulation systems. High-grade brain tumours, such as glioblastoma multiforme (GBM) represent a paradigm of locally initiated haemostatic abnormalities that propagate systemically, likely through circulating mediators, such as extracellular vesicles and soluble factors. Reciprocally, CAT impacts the biology of cancer cells and may drive tumour evolution. The constituent, oncogene-transformed cancer cell populations form complex ecosystems, the intricate architecture of which has been recently revealed by single cell sequencing technologies. Amidst this phenotypic heterogeneity, several alternative pathways of CAT may exist both between and within individual tumours and their subtypes, including GBM. Indeed, different contributions of cells expressing key coagulant mediators, such as tissue factor, or podoplanin, have been identified in GBM subtypes driven by oncogenic mutations in EGFR, IDH1 and other transforming genes. Thus, a better understanding of cellular sources of CAT, including dominant cancer cell phenotypes and their dynamic shifts, may help design more personalised approaches to thrombosis in cancer patients to improve outcomes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose
/
Neoplasias Encefálicas
/
Glioblastoma
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Thromb Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá