Interdisciplinary Research in the areas of cancer genomics and bioinformatics, cancer biology and genetics, cancer drug discovery and pharmacology as well as clinical trial expertise. Choices of programs will be driven by unequivocal evidence of their role in disease control and treatment in clinically relevant settings. The clinical Division consists of a team of highly trained physicians and staff with extensive experience in internal medicine, cancer treatment, translational medicine, Phase 0-I, early phase II clinical trials and clinical pharmacology research. Our clinical research platform is based on: 1. The speed and efficiency of the design, launch, and conduct of trials; 2. The innovation in science and trial design with strong translational background; 3. Trial prioritization, selection, support, and completion; 4. Dedicated clinical, pathology and laboratory platform integrated with a molecular screening program. Facilities of the Division include Ambulatory Service for patients screening: 3 days per week (24 slots). Outpatients Day Hospital Service for patient treatment: 3 days per week (33 slots). In patients hospitalization: 36 beds for patients on phase I studies and for critical patients with adverse events following experimental treatment. Research Nurses / Study Coordinators The Research Staff consists of Research Nurses and Study Coordinators who are responsible for protocol management and patient care. Our research staff is responsive to both patient and study sponsor needs. Each study is assigned a research team member to ensure continuity of care for study patients as well as the needs of the study sponsor. The research staff is closely involved with patient screening, enrollment, education, and patient follow up. They maintain constant communication with study sponsors, physicians, clinical
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staff, and patients. Annually trained on ICH GCP, Clinical trial procedures, regulatory questions as well as on specific pathologies, our team provides in-depth therapeutic expertise at every level of your study process.
being offered include the isolation, enumeration, and genotyping of circulating tumor cells, determination of plasma cytokine levels, and genotypic analysis of plasma-based tumor DNA. All these technologies are applied in clinical trials.
Early Drug Development Research Program Early drug development research program is equally committed to scientific discovery and patient care. Our world-class young clinical investigators work across disciplines, departments, and institutional boundaries to translate research findings into new diagnostics and therapeutics for patients. The cornerstone of translational research of medical oncology staff is collaboration: close interactions among basic scientists, computational biologists, chemists, clinical investigators, and others. The group also enjoys fruitful partnerships with pharmaceutical and biotechnology companies, which have the complementary resources needed to help transform promising compounds into drugs and biologics. A major departmental research theme is linking knowledge of the genes that cause cancer to the discovery and testing of new therapeutics, involving both small-molecule drugs and immune approaches. Other key themes relate to developing personalized medicine strategies by using genetic, epidemiologic, and population-based studies to determine risk and ideal treatment for individual patients. The early drug development team currently has nearly 40 open adult therapeutic clinical trials. It accrues several patients to therapeutic and non-therapeutic clinical protocols each year. Disease center members play a major role in the IEO research programs and in international cooperative group trials, such as the International Breast Cancer Study Group (IBCSG) and the Breast International Group (BIG). Department investigators focus on testing new drugs in Phase I and II trials, particularly firstin-human studies that have the potential to move the boundaries of solid tumors oncology care. Technologies
The milestones of our clinical research are here summarized: 1. Identification of biological features of disease predictive of response to a target-oriented approach within a molecular screening program. 2. Identification of mechanisms of resistance to antiHER2 positive breast cancer disease and development of new strategies to target HER2 positive breast cancer. 3. Molecular screening with next generation sequencing technologies to evaluate potential “molecular drivers” of resistance to standard treatments in patients with luminal B and triple negative breast cancer. 4. Exploring the combination of endocrine therapy with biological agents targeting HER2, src or insulin growth factor receptor (IGFR). 5. Exploring the role of dual targeting (multiple antibodies or antibodies conjugated to chemotherapeutics agents) in patients with HER2 positive breast cancer. 6. Generation of human-xenograft models to predict response to targeted agents in patients with metastatic breast cancer. 7. Selecting cancer vaccine targets for individual cancers. Analyzing the immunogenicity of T-cell and B-cell peptide epitopes and performing cytokine immune assessments to identify epitopes and cytokines that enhance immune responses. 8. Exploring the role of antigen specific immunotherapeutics for patients with triple negative breast cancer with residual disease after a neoadjuvant chemotherapy.
Future research should achieve the goal to recognizing the diversity of targets in each subtype of breast cancer, taking advantage from molecular characterization tools. New prospective trials will specifically address the questions of targeting multiple pathways in each breast cancer subtype, to maximize response to treatment and minimize the toxicity. Recent large-scale tumor sequencing studies, including wide genome analysis studies, have identified a number of mutations that might be involved in breast cancer tumorigenesis. Analysis of the frequency of specific mutations across different tumors has been able to identify some, but not all of the mutated genes that contribute to tumor initiation and progression. One reason for this is that other functionally important genes are likely to be mutated more rarely and only in specific contexts. Thus, for example, mutation in one member of a collection of functionally related genes may result in the same net effect, and/or mutations in certain genes may be observed less frequently if they play functional roles in later stages of tumor development, such as metastasis. The biggest challenge for the future will be to apply a network reconstruction and coexpression module identification-based approach to identify functionally related gene modules targeted by somatic mutations in cancer. The ultimate goal of this approach is to identify network of pathways and potential crosstalks within pathways. Dual or multiple targeting in order to shutdown “drivers” pathways will be the future of breast cancer treatment within several subtypes. This method was applied to available breast cancer sequence data, and identified several pathways as targets of rare driver mutations in breast. These mutations do not appear to alter genes that play a central role in these pathways, but rather contribute to a more refined shaping or “tuning” of the functioning of these pathways in such a way as to result in the inhibition of their tumor-suppressive signaling arms, and thereby conserve or enhance tumor-promoting processes.
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