By Sara Ek, Lund University
It’s been known for a while that different types of cancers require different types of treatments and the work to divide cancer into meaningful subgroups is far from finished. The major efforts today focus on changing the way patients are grouped. This strategy may ultimately help provide better treatment options within subgroups.
Conventionally, subgrouping methods, like morphology or histology, are based on observing the (biopsied) tumour tissue — the visual appearance of the cells and structures. Although these methods still are the gold standard for routine diagnostics, new methods are being developed to correlate the presence of individual or groups of biomolecules in the tumour tissue with clinical features. Such clinical features include how well a patient responds to treatment and how long a patient survives after diagnosis and, if successful, would allow a more functional and clinically useful subgrouping.
Recently, it has been discovered that the biomolecule SOX11 can be used for subgrouping patients with blood cancer (like lymphoma, leukaemia, myeloma) or ovarian cancer and also for identifying patients with different survival and time to relapse. According to studies published in DNA Research in 1999 by Azuma et al. and in Genes & Development in 2006 by Bergsland et al., SOX11 is a biomolecule that is essential for the development of the central nervous system (CNS) in the foetus. It has also been shown that brain tumours produce this biomolecule — for example, in medulloblastoma (as shown by Lee et al., 2002) and malignant glioma (as shown by Weigle et al., 2005).
Using advanced analyses, we were able to show that SOX11 is present in tumour tissues not deriving from the CNS, such as tissues in blood and in ovarian cancer. We also developed an antibody, a molecule able to specifically bind other biomolecules, particularly to SOX11. This antibody is able to analyze the presence of SOX11 in tumour tissue using routine diagnostic equipment, which is available at all major hospitals. Previously, commercially available antibodies had none of the necessary characteristics to be used in routine diagnostics. In addition, our developed antibodies were shown to be of use in predicting the survival and time to relapse for blood cancer (work done at the Karolinska Instituet) and ovarian cancer (our group), respectively.
Blood cancers consist of many subtypes, based on the malignant morphology of certain blood cells, some of which currently carry a poor prognosis. According to latest statistics published by the U.S. National Cancer Institute (www.cancer.gov), one type of blood cancer, non-Hodgkin’s lymphoma, has an estimated 56,980 new cases, diagnosed in 2009, along with 19,500 disease-related deaths. One of the subtypes with the poorest survival is mantle cell lymphoma (MCL). This malignancy needs an early and accurate diagnosis followed by an aggressive therapy to prolong patient survival. SOX11 is a highly specific marker for MCL and we demonstrated that it can be used to diagnose this subtype efficiently. SOX11 has also been shown to predict survival by our collaborators at the Karolinska Institutet (Wang et al., Br J Haematol 2008). Our most recent data also show that SOX11 prevents tumor cell growth (data published in 2010, Molecular Cancer). Ongoing research will clarify the role of SOX11 in regulating tumour growth. Hopefully this will enable the development of new treatment options based on SOX11.
Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecological malignancy and the fifth most common cause of cancer-related death in women. In 2009, it is estimated that 21,550 new ovarian cancer cases will be diagnosed in the U.S. and that 14,600 will succumb to the disease (source: National Cancer Institute). There is clearly an urgent need to improve our understanding of the molecular mechanisms underlying EOC as well as to develop better prognostic and predictive assays and to identify new therapeutic targets.
Our results show that SOX11 is a biomolecule that can be used successfully to functionally divide patients afflicted with blood or ovarian cancer into subgroups and thus may be used in the future to select a better and more appropriate therapy for individual patients. The presence of SOX11 in other types of malignancies, such as breast, lung and brain tumours indicate that SOX11 may have a widespread functional role in several major types of cancers.
Sara Ek
Lund University
www.atomiumculture.eu
Hay 0 Comentarios