Study Highlights Potential Drug Target for One in Ten Breast Cancers
CANCER RESEARCH UK scientists have discovered how a key protein fuels breast cancer growth by boosting numbers of cancer stem cells in tumours that have low levels of a protein called claudin, accounting for up to 10 per cent of all breast cancers.
This raises the prospect that treatments currently being developed to inhibit this key protein – called Transforming Growth Factor Beta (TGF-beta) – could be used to treat this group of women, who tend to have poorer survival and for whom there are currently no targeted treatments.
The study is published in Nature Communications today (Tuesday).*
Earlier this year the same team, from Cancer Research UK’s Cambridge Research Institute, published a groundbreaking study showing that breast cancer was not one disease, but ten, each defined by its own unique ‘genetic fingerprint’.**
In this study they used this knowledge to explore, for the first time, how the network of genes activated by TGF-beta differs among different types of breast cancer.
This revealed that, in cancers with low levels of the protein claudin, TGF-beta activates a specific network of genes that boosts the number of breast cancer stem cells – which promote cancer spread and are associated with poor survival.
TGF-beta does this through the regulation of two other proteins – Smad and SRF – and with the help of a third – NEDD9 – which helps to assemble the three into their active form.
Dr Alejandra Bruna, senior author on the study, said: “For years scientists have been puzzling how TGF-beta can be seen to both fuel and suppress the growth of cancer. And now, thanks to the improved understanding we are building of the different genetic types of breast cancer, we can pinpoint one of the specific pathways that account for these differences.”
Study leader Professor Carlos Caldas, added: “Crucially this study highlights the role of TGF-beta in one particular subtype that accounts for up to 10 per cent of all breast cancers. A number of promising treatments are already in early phase trials to target TGF-beta, meaning there is genuine hope of improved treatment options for this group of women in the near future. The next step will be to design the appropriate clinical trials.”
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “This study provides us with important insights into TGF-beta’s ‘split personality’ and how it can both prevent and fuel the growth of cancer cells. Our scientists have been at the forefront of research into the role of growth factors in cancer and it’s immensely heartening to see this now paving the way for powerful new treatments with the potential to benefit patients.”
For media enquiries, please contact Ailsa Stevens in the Cancer Research UK press office on 020 3469 8309 or, out of hours, the duty press officer on 07050 264 059.
Notes to editors:
* Bruna A. et al, TGFβ induces the formation of
tumour-initiating cells in caludinlow breast cancer, Nature
Communications, 2012, DOI: 10.1038/ncomms2039
** In April this year Professor Carlos Caldas and colleagues published findings from the largest global gene study of breast cancer tissue ever performed. The study, known as METABRIC, reclassified the disease into 10 completely new categories based on the genetic fingerprint of a tumour. For more information see: http://www.cancerresearchuk.org/cancer-info/news/archive/pressrelease/2012-04-18-breast-cancer-rule-book-rewritten
About the Cambridge Research Institute
The Cancer Research UK Cambridge Research Institute is a major new research centre which aims to take the scientific strengths of Cambridge to practical application for the benefit of cancer patients. The Institute is a unique partnership between the University of Cambridge and Cancer Research UK. It is housed in the Li Ka Shing Centre, a state-of-the-art research facility located on the Cambridge Biomedical Campus which was generously funded by Hutchison Whampoa Ltd, Cambridge University, Cancer Research UK, The Atlantic Philanthropies and a range of other donors. For more information visit www.cambridgecancer.org.uk.
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Posted: September 2012