HypOxygen's Blog - Latest News from HypOxygen

Hypoxia and the Hallmarks of Cancer: Sustaining Growth and Resisting Cell Death

Of all the “Hallmarks of Cancer” defined by Hanahan and Weinberg, the ability to proliferate indefinitely is often considered to be the most central to cancer’s core features. Sustaining Growth and Resisting Cell Death enable cancer cells to override signaling that ensures normal tissues’ homeostasis of numbers and size. Previous chapters in our mini-series on “Hypoxia and the Hallmarks of Cancer” have showcased Avoiding Immune Destruction and Tumor Promoting Inflammation and Genome Instability and Mutation and Enabling Replicative Immortality as well as Inducing Angiogenesis and Activating Invasion and Metastasis.

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Hypoxia and the Hallmarks of Cancer: Angiogenesis and Metastasis

Hanahan and Weinberg’s “Hallmarks of Cancer” are at the root of the multi-step progression of cancer, and they are all influenced by hypoxia in the tumor microenvironment. In this mini-review series, HypOxygen has been taking a closer look at the way HypOxystation users worldwide are delineating the effects of hypoxia on the Hallmarks of Cancer: so far, we’ve showcased Avoiding Immune Destruction and Tumor Promoting Inflammation and Genome Instability and Mutation and Enabling Replicative Immortality.  

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Hypoxia and the Hallmarks of Cancer: Genome Instability and Immortality

HypOxygen continues to look at the way the iconic “Hallmarks of Cancer”, as first described by Douglas Hanahan and Robert Weinberg, are influenced by hypoxia in the tumor microenvironment. Oxygen around and within the tumor cells is central to metabolism, immunology, epigenetics and therapy resistance of all the cancers; in the lab, oxygen levels during tumor cell culture exert effects on metabolism, maintenance, cell yield, and cell survival. 

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Hypoxia and the Hallmarks of Cancer: Inflammation and Immunity

The iconic “Hallmarks of Cancer” first described by Douglas Hanahan and Robert Weinberg in 2000 continue to develop explosively as efforts to illuminate the “acquired capabilities of cancer” evolve. Hypoxia in the fast-growing, poorly perfused tumor setting is one of the main factors selecting for survival of cancer cells and driving mutagenesis and metastasis. Oxygen in the tumor microenvironment and within the cells is central to metabolism, immunology, epigenetics and therapy resistance of all the cancers.  

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Don Whitley Visits The Francis Crick Institute

DWSCrickDr Don Whitley, chairman and founder of DWS, recently visited The Francis Crick Institute in London to see the recently installed Whiltley H45 Hypoxystation at the site. 

The Crick has moved into a brand new state-of-the-art building in the centre of London. Situated next to Kings Cross and St Pancreas stations, The Crick brings together 1500 scientists and staff working collaboratively in the biggest biomedical research facility under one roof in Europe. The work at The Crick covers many disciplines and applications in biomedical research, all with the aim of improving understanding of human health and disease. 

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Therapeutic Targeting of Hypoxia and HIF's in Cancer

“Tumor hypoxia and HIF’s affect most of the cancer hallmarks … and contribute to chemo- and radiotherapy resistance.” In their review from 2016, Wigerup, Pahlman and Bexell of Lund University in Sweden discuss how hypoxia inducible factors HIF’s regulate the hypoxic microenvironment in cancer, and the therapeutic strategies that are being developed to improve patients’ prognosis. Dr. Sven Pahlman’s lab has been using the H35 HypOxystation for more than 5 years now, to research SCLC and neuroblastoma, and their data is contributing to the understanding of the role of oxygen levels in the progression of cancer.

Hypoxia and HIF-1α and 2α expression in cancer usually signify a worse prognosis, but most hypoxia-induced transcriptional, translational, and epigenetic changes are cell-type specific. Many effects engendered by hypoxia are mediated directly or indirectly via HIF pathways, and most are causative of the iconic “Hallmarks of Cancer” that Hanahan and Weinberg introduced in 2000 and expanded in 2011. Hypoxia induces increased autophagy, apoptosis, and aberrant cell proliferation; neoangiogenesis mediated by VEGF and PDGF-β; proliferation of cancer stem cells; metabolic reprogramming to satisfy energy and synthetic requirements in proliferating cells; modulation of inflammation and immune responses; genomic instability through increased mutagenesis and diminished DNA repair; and metastasis as hypoxia induces epithelial-to-mesenchymal transition and degradation of the extracellular matrix. Assaying the relationship between hypoxia and the Hallmarks of Cancer benefits significantly from the physiological atmosphere mimicked in the HypOxystation, a closed-culture hypoxia workstation controlling gasses, temperature and humidity.

Read more: Therapeutic Targeting of Hypoxia and HIF's in Cancer