diagnostics – Drug Discovery Opinion

FSH Receptors Outline Tumours

Researchers at Mount Sinai School of Medicine and France’s National Institute of Health and Medical Research (INSERM) have discovered a biomarker that could be applicable to a range of different cancers.

In a study of more than 1300 patients, the team found that the follicle stimulating hormone (FSH) receptor – which is normally present only at low levels in the blood vessels or the granulosa cells of the ovary and the Sertoli cells of the testis – is also expressed at higher levels in eleven different types of cancer. The receptor was absent in other normal tissues, including normal tissue from the organ bearing the tumour. Not only does the FSH receptor appear to be specific for endothelial cells in the vasculature surrounding tumour tissues, it is also present from the very early stages and is easily detectable using conventional imaging methods. In most cases, the blood vessels expressing FSH receptors were at the periphery of the tumour, in a layer about 10mm thick, making it a good target for improving cancer detection and also guiding surgery and radiation treatment. Blocking FSH receptor signalling, which stimulates angiogenesis via up-regulation of vascular endothelial growth factor, could also potentially provide a new strategy for developing anticancer drugs.

The study is published in The New England Journal of Medicine.

New Breast Cancer Subtype

Gene expression profiling is used to guide treatment options for women with breast cancer. Endocrine therapies – tamoxifen or aromatase inhibitors – are offered to women whose cancer is oestrogen receptor (ER) positive whilst the monoclonal antibody, trastuzumab (Herceptin®) and the small molecule, lapatinib (Tykerb®) are used to treat women whose cancer overexpresses the HER2 receptor. About 15% of breast cancers – the so-called triple negative breast cancers that don’t have receptors for oestrogen, progesterone or HER2 – don’t respond to hormone therapy or to HER2 blockers and the prognosis for women with these cancers is relatively poor.

Researchers at Washington University University School of Medicine in St. Louis have now identified a gene that is overexpressed mainly in ER-negative, HER2-negative and triple negative breast cancers, leading to the possibility of a new clinical biomarker and potential treatments. Upregulation of Wnt signalling coreceptor, LRP6 (low-density lipoprotein receptor-related protein 6), was found in about a quarter of the breast cancer samples that the researchers examined. Previous studies had shown that the protein Mesd (mesoderm development) blocks LRP6 and was able to slow the growth of cultured breast cancer cells. Mesd also inhibits the development of mammary tumours in mice, without producing known pathway-dependent side-effects such as bone lesions, skin disorders or intestinal malfunctions. A smaller fragment of Mesd was found to be as effective as full length Mesd and to have improved stability.

The study is published in the Proceedings of the National Academy of Sciences.

Although the study offers the prospect of targeted therapy for women with breast cancer that is currently difficult to treat, both screening and prescribing practices need to improve for such discoveries to realise their full potential. A recent news feature in Nature Biotechnology highlights differing views on testing as well as the problems associated with diagnostic tests for HER2 – both of which may be compromising women’s access to appropriate and effective treatment.

Blood Test for Alzheimer’s Disease Moves a Step Nearer

blood test There is no single test that will diagnose Alzheimer’s disease (AD) and a diagnosis of possible or probable AD is currently based on neuropsychological tests together with advanced brain imaging techniques such as functional MRI or PET scans. Simple and reliable diagnostic tests for AD are much needed, and researchers at the University of Georgia have now shown that the levels of two antibodies in the blood correlate with the severity of AD symptoms and may provide just such a test. The team had previously shown that levels of anti-Aβ and anti-RAGE antibodies were significantly higher in AD patients than in healthy individuals and the latest study reveals a direct relationship between the severity of disease and the levels of the two antibodies. Much evidence points to a link between AD and elevated levels of β-amyloid (Aβ) peptides. Binding of Aβ to neuronal membrane receptors for advanced glycation end products (RAGE) is believed to trigger inflammation and contribute to the neurological damage characteristic of AD.

Although it could be years before a diagnostic test based on their work is available for clinical use, the researchers hope that it will, one day, provide a way of identifying people with early AD and those at risk of developing the disease. The study is published in full in The Journals of Gerontology.