Mission and Vision There is an impelling need to speed up the transfer of scientific results from the laboratory to the clinic: clinicians require it, society demands it, and scientists must respond. Each interest group depends on the other two to achieve this aim. This is why we established the Molecular Medicine for Care (MMC) program at IEO. Through the mutual collaboration of scientists, clinicians and patients, we are driving discoveries from the basic research programs conducted in the laboratory of Pier Paolo Di Fiore [1-11] into the clinical domain, through four scientific programs that focus on breast, lung and ovarian cancers. While these are being carried forward, we have brewing in the pipeline a number of other new discovery projects that will ultimately translate into the improved clinical management of breast, lung, ovarian and prostate cancer. Our current scientific programs aim to: 1) Identify stem cell markers for the diagnosis, prognosis and therapeutic stratification of breast, lung and ovarian cancers.

2) Develop a blood test for the early diagnosis of lung cancer. 3) Understand breast and ovarian cancer for early diagnosis.

4) Make new discoveries to increase our molecular understanding of cancer and feed new translational research projects. MMC Scientific Programs Stem cell markers for the diagnosis, prognosis and therapeutic stratification of breast, lung and ovarian cancer Lead scientific contacts Breast cancer: Salvatore Pece, Fabrizio Bianchi, Stefano Confalonieri, Manuela Vecchi Lung cancer: Elena Belloni Ovarian Cancer: Ugo Cavallaro Stem cells are a rare population of cells necessary for tissue integrity and regeneration in case of injury. Their numbers within any normal tissue are very tightly controlled, but it is now widely accepted that these restraints can malfunction in cancer, leading to an inappropriate expansion of stem cell populations. We discovered that genes expressed in breast stem cells can be used as biomarkers to improve the stratification of breast tumors according to their pathological, molecular and clinical characteristics [3]. Kak sdelat kupol dlya cerkvi iz bumagi. However, the original stem cell signature we identified contained too many genes to be of clinical use. Therefore, we are now developing a smaller stem cell profile that still retains the predictive features of the stem cell profile, but that can be analyzed more easily in a clinical setting using immunohistochemistry or quantitative PCR analysis.

Molecular Medicine for Care Program (MMC) Director. Pier Paolo Di Fiore +5.198 +5.991; pierpaolo.difiore@ieo.eu; Mission and Vision. There is an impelling need to speed up the transfer of scientific results from the laboratory to the clinic: clinicians require it, society demands it, and scientists must respond.

We are assessing the ability of these biomarkers to classify breast tumors according to aggressiveness, associated metastatic risk and therapeutic response to hormonal and/or chemo-/radio-therapy. Ultimately, we aim to develop a clinical test that will fine-tune the current diagnostic/prognostic ability of clinicians and to improve the clinical management of breast cancer. Using a similar approach to that pursued for breast [3], we are now trying to identify and isolate cells with stem properties in non-small cell lung cancer (NSCLC) and in ovarian cancer, for which stem cell identity remains poorly defined. The identification and characterization of the cells that initiate, sustain, and disseminate lung tumors should create new opportunities for the early detection and/or improved treatment for these diseases.

Development of a blood test for the early diagnosis of lung cancer Lead scientific contacts Fabrizio Bianchi The absence of national screening programs for lung cancer, and the lack of symptoms in early stage disease means that the detection of early lung cancer is difficult. The development of clinical tools for the early diagnosis of lung cancer is, therefore, a pressing clinical necessity, particularly for at-risk subjects (smokers or ex-smokers, aged 50 years or more).

We have previously identified and validated in independent patient cohorts a circulating miRNA signature (based on 34 miRNA species) that can be used in a blood test to detect early stage lung cancer in asymptomatic patients [1]. In collaboration with theDivision of Thoracic Surgery and the Division of Radiology, we are currently assessing the clinical applicability of this test through its large-scale validation in a prospective multicenter trial launched by the Lung Cancer Early Detection Unit in September 2012 (COSMOS II). The trial has already recruited close to 6,000 of the planned 10,000 patients. If effective, this blood test will be significantly cheaper and easier to apply in national lung cancer screening programs than the only currently available clinical test, which is based on low-dose computer assisted tomography screening. Understanding breast and ovarian cancer for early diagnosis Lead scientific contacts Breast cancer: Fabrizio Bianchi Ovarian Cancer: Ugo Cavallaro, Fabrizio Bianchi This scientific program is designed to investigate whether prognostic/diagnostic miRNA profiles exist for breast and ovarian cancers.