期刊
CANCER LETTERS
卷 492, 期 -, 页码 1-10出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.07.004
关键词
Intratumoral heterogeneity; Hypoxia; Immune escape; Tumor resistance; Antitumor immunity; Tumor plasticity; DNA repair; Epigenetics
类别
资金
- INSERM
- Institut National du Cancer [PLBIO15-266, INCa-DGOS-PRT-K]
- Alliance nationale pour les sciences de la vie et de la sante (AVIESAN)
- Research Council of Norway through it's Centres of Excellence funding scheme [223250]
- Sheikh Hamdan Medical Award [MRG-230/2017-2018]
- FRIPRO Mobility Grant Fellowship from the Research Council of Norway - EU's Seventh Framework Programme's Marie Sklodowska Curie Actions (MSCA COFUND) [608695]
- Legat for Forskning av Kreftsykdommer fund at University of Bergen (UiB)
- Familien Blix fund
While it is widely accepted that high intratumoral heterogeneity confers serious challenges in the emerging resistance and the subsequent effective therapeutic targeting of cancer, the underlying biology of intratumoral heterogeneity remains elusive. In particular, it remains to be fully elucidated how microenvironmental factors shape genetic and non-genetic heterogeneity, which in turn determine the course of tumor evolution and clinical progression. In this context, hypoxia, a hallmark of most growing cancers, characterized by decreased O-2 partial pressure is a key player of the tumor microenvironment. Despite extensive data indicating that hypoxia promotes cellular metabolic adaptation, immune suppression and various steps of tumor progression via hypoxia regulated gene transcription, much less is known about the role of hypoxia in mediating therapy resistance as a driver of tumor evolution through genetic and non-genetic mechanisms. In this review, we will discuss recent evidence supporting a prominent role of hypoxia as a driver of tumor heterogeneity and highlight the multifaceted manner by which this in turn could impact cancer evolution, reprogramming and immune escape. Finally, we will discuss how detailed knowledge of the hypoxic footprint may open up new therapeutic avenues for the management of cancer.
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