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An International 'Dream Team' Against Breast Cancer Headed By Vall DíHebron, VHIO and SOLTI

by Rukmani Krishna on September 22, 2012 at 12:07 AM
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 An International 'Dream Team' Against Breast Cancer Headed By Vall DíHebron, VHIO and SOLTI

A multi-centre international study involving four Spanish and three North American research centres* is being headed by an academic breast cancer research group. The Vall d'Hebron Breast Cancer Unit, the Vall d'Hebron Institute of Oncology (VHIO) and SOLTI are heading the study. The aim of the study is to investigate whether BKM120, a drug that inhibits the PI3K pathway (phosphatidylinositol-3-Kinase) can be an effective treatment against triple-negative breast cancer.

At present it is known that breast cancer can be classified into different subtypes with varying prognoses and responses to treatment. This classification is essentially based on the presence of hormone receptors (oestrogen and progesterone) and the HER2 receptor. In clinical practice this has led to the development of increasingly selective and optimal treatments for patients. Advances in breast cancer treatment using new drugs on accurately-selected populations, along with the implementation of public screening programs, have contributed in recent years to reducing mortality from this disease.

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Triple-negative breast cancer: the most aggressive formTriple-negative breast cancer is defined by the absence of hormone receptors and HER2. This type of breast cancer is an aggressive variety of the disease that generally appears in younger women. Few treatment options beyond chemotherapy and anti-angiogenic agents are currently available. The present study aims to test whether BKM120 is effective for these patients and also, by means of biomarkers in the blood or in the tumour, identify which tumours respond to this new treatment.

The design initiative for this study falls within the grant awarded by the organization Stand Up to Cancer (SU2C), a non-profit entity whose objectives include supporting translational cancer research to ensure that the benefits of the most innovative treatments resulting from basic research can rapidly reach patients through study designs that allow fast-track application of the results.
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"Dream Teams" against cancerSU2C promotes the formation of multidisciplinary teams, known as "Dream Teams", which bring together the talent and knowledge of top scientists and cancer specialists from all over the world, bringing added value to research and allowing the rapid transfer of findings from basic research to clinical application.

Each Dream Team is made up of leading experts in certain tumour types and receives funding to develop their respective project over a three-year period in a highly collaborative and independent environment. The removal of bureaucratic barriers prevents part of the funding being lost through intermediaries, allowing experts to concentrate exhaustively on their research. This structure has been designed to obtain the optimum results with the highest assurance in the shortest possible time.

The team of Dr Josť Baselga from the VHIO is one of the Dream Teams selected by SU2C to take part in this ambitious project and head up the study on BKM 120 for the treatment of triple-negative breast cancer. This top-level collaboration stems from the experience and knowledge of the groups of excellence in the Breast Cancer Unit and the Research Unit for the Molecular Therapy of Cancer - "la Caixa" at the VHIO, headed respectively by Dr Javier Cortťs and Dr Jordi Rodůn, as well as the expertise of SOLTI in coordinating multi-centre academic studies.

The Research Unit for the Molecular Therapy of Cancer (UITM) "la Caixa" and the Breast Cancer Unit already boast four years' experience in researching a broad spectrum of PI3K pathway inhibitors. They recently presented a study at the Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, June 1 - 5, 2012, on the actions of these drugs in patients suffering from breast cancer, in monotherapy or in combination with other treatments. "This study, with data from the largest patient sample ever used, presents some encouraging findings with regard to the control time of the disease in metastatic patients," explains Dr Cristina Saura, the study coordinator in Spain as a member of SOLTI.

Innovations in breast cancer treatmentThe PI3K pathway regulates key cellular functions such as cell growth, proliferation and survival. The appearance of mutations in this pathway is common and seems to contribute to the development of certain types of cancer in women, such as cancers of the breast, ovaries, uterus and endometrium. These mutations have also been implicated in the resistance mechanisms to certain conventional treatments (chemotherapy, hormone treatment or Trastuzumab).

The study that is already underway and open at the Vall d'Hebron University Hospital is a Phase II trial with a specific PI3K pathway inhibitor - the molecule BKM120 - and "the trial aims to determine the clinical activity of the molecule in patients with triple-negative metastatic breast cancer at an advanced stage of the disease still progressing following treatment with chemotherapy," comments Dr Javier Cortťs, the Head of the Breast Cancer Unit, and continues, "we are thus talking about advanced disease treatment, when the tumour has progressed to standard treatment options".

One of the novel aspects of this project is that it has been specifically designed to determine, by an analysis of the genetic profiles of patients, whether there is an identifiable subgroup of patients that particularly responds to this treatment. "The analysis of the genetic profiles of patients who respond and those who don't will help us to understand the reasons for this response, thanks to the technology and specialist knowledge that only this Dream Team possesses, which gives it a unique value," explains Dr Rodůn, Head of the UITM and principal researcher of this international study.

The study with BKM120 is an example of how the highest level of technology combined with excellence in biomedical research can translate into major benefits for patients. Future lines of research will be directed at the exploration and validation of new predictive biomarkers, bringing us one step closer to realising the promise of personalized medicine. It is becoming increasingly necessary to search for biomarkers of response to these molecules in order to determine, prior to treatment, which patients are going to benefit from this treatment and why.

Source: Eurekalert
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