Clinical implications of intratumor heterogeneity: challenges and opportunities

被引：321

作者：

Ramon y Cajal, Santiago ^{[1
,2
,3
,4
]}

Sese, Marta ^{[1
,3
]}

Capdevila, Claudia ^{[1
,5
]}

Aasen, Trond ^{[1
,3
]}

De Mattos-Arruda, Leticia ^{[6
]}

Diaz-Cano, Salvador J. ^{[7
,8
]}

Hernandez-Losa, Javier ^{[1
,2
,3
]}

Castellvi, Josep ^{[1
,2
,3
]}

机构：

[1] Univ Autonoma Barcelona, Vall dHebron Inst Res VHIR, Translat Mol Pathol, Passeig Vall dHebron 119-129, Barcelona 08035, Spain

[2] Vall dHebron Hosp, Dept Pathol, Passeig Vall dHebron 119-129, Barcelona 08035, Spain

[3] Spanish Biomed Res Network Ctr Oncol CIBERONC, Barcelona, Spain

[4] Autonomous Univ Barcelona, Vall dHebron Univ Hosp, Dept Pathol, Pg Vall dHebron 119-129, Barcelona 08035, Spain

[5] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA

[6] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, C Natzaret 115-117, Barcelona 08035, Spain

[7] Kings Coll Hosp London, Dept Histopathol, London, England

[8] Kings Hlth Partners, London, England

来源：

JOURNAL OF MOLECULAR MEDICINE-JMM | 2020年 / 98卷 / 02期

关键词：

Intratumor heterogeneity; Liquid biopsy; Artificial intelligence; Antitumor therapeutics; CIRCULATING TUMOR DNA; SOMATIC DOWN-REGULATION; BREAST-CANCER; GENE-EXPRESSION; LUNG-CANCER; 4E-BINDING PROTEIN-1; CLONAL EVOLUTION; LIQUID BIOPSIES; POOR-PROGNOSIS; PAN-CANCER;

D O I：

10.1007/s00109-020-01874-2

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In this review, we highlight the role of intratumoral heterogeneity, focusing on the clinical and biological ramifications this phenomenon poses. Intratumoral heterogeneity arises through complex genetic, epigenetic, and protein modifications that drive phenotypic selection in response to environmental pressures. Functionally, heterogeneity provides tumors with significant adaptability. This ranges from mutual beneficial cooperation between cells, which nurture features such as growth and metastasis, to the narrow escape and survival of clonal cell populations that have adapted to thrive under specific conditions such as hypoxia or chemotherapy. These dynamic intercellular interplays are guided by a Darwinian selection landscape between clonal tumor cell populations and the tumor microenvironment. Understanding the involved drivers and functional consequences of such tumor heterogeneity is challenging but also promises to provide novel insight needed to confront the problem of therapeutic resistance in tumors.

引用

页码：161 / 177

页数：17

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