Suffocating pancreatic cancer stem cells

Suffocating pancreatic cancer stem cells

Targeting stem cell metabolism and cutting off their oxygen - a new therapeutic option

Centre for Stem Cells in Cancer & Ageing

Stem Cells in Cancer

The BCI pioneers a Centre for Stem Cells in Cancer & Ageing that spans both molecular and patient biology to address the twin issues of cancer and ageing in cancer (stem) cells and in people. Building on our established strength in stem cell biology, we will further expand our laboratory programme to important aspects of our ageing patient population including age-related co-morbidities.

Our interdisciplinary and complementary research programme integrates CSC biology with other BCI groups working on tumour initiation, the microenvironment & inflammation, stem cell biology, drug discovery, and early clinical trials (see below). Our work funded by the ERC advanced investigator grant over the past 5 years has contributed to an improved understanding of CSC biology and function, and set the stage for comprehensive characterisation of CSCs and their microenvironment.

Our interest in using novel technologies to foster diagnosis and treatment of patients with cancer has lead to collaborations with bioengineers at QMUL and beyond (e.g. nanoparticles, microfluidics, bioreactors, lab-on-a-chip), including translational projects with Physician-Scientists at the Barts NHS Trust. Our CSC-centred drug response screening platform ScanCSCTM and its further evolution provides a strong basis for precision medicine approaches with this support.

Cancer & Ageing

In the UK, 155,000 people aged 70+ years are diagnosed with cancer every year representing 50% of all cancer diagnoses, a number likely to rise as the population ages. Survival rates for older cancer patients lag behind younger patients with the same cancers. We face new problems in understanding the biology of older people who develop cancer, which also includes, but is not limited to, important co-morbidities such as diabetes and metabolic syndrome.

Group Leaders in the Centre

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Life in the Centre

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Results & Discoveries

Recent highlights from our research

  • We have discovered that pancreatic cancer is hierarchically organised and cancer stem cells (CSCs) represent the root of this disease driving tumour progression, metastasis and chemoresistance.
    Hermann et al. Cell Stem Cells 2007 (cited 1662x), Lonardo et al. Cell Stem Cell 2011, Sainz et al. Cancer Cell 2013, Miranda et al., Nature Methods 2014, Cioffi et al. Gut 2015, Raj et al. Stem Cells 2015
  • We have also identified that the tumour microenvironment acts as a CSC-promoting entity further enhancing their invasiveness and chemoresistance.
    Lonardo et al. Cell Cycle 2012, Sainz et al. Cancer Res 2014, Sainz et al. Gut 2015
  • We have shown that pharmacological or genetic elimination of CSCs results in increased survival in preclinical mouse models.
    Mueller et al. Gastroenterology 2009, Lonardo et al. Cell Stem Cell 2011, Cioffi M et al. Clin Cancer Res 2015, Hermann et al. Gastroenterology 2014, Zagorac et al. Cancer Res 2016
  • Pancreatic CSCs bear an epigenetically defined gene expression signature resulting in a distinct metabolic phenotype and immune privilege.
    Sancho et al. Cell Metabolism 2015, Sancho et al. BMC 2016

Building on these original findings and newly developed technologies in our lab, we are now seeking common key regulators that control stemness and immune evasion in pancreatic CSCs using functional genomics.

We are dissecting mechanisms of action and developing multimodal treatment strategies that also target CSCs.
This should lead to more durable treatment response and prevent relapse.


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