How Will Genomics Change Our Practice? Paula Trahan Rieger RN, MSN, CAE, FAAN CEO, Oncology Nursing Society

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1 How Will Genomics Change Our Practice? Paula Trahan Rieger RN, MSN, CAE, FAAN CEO, Oncology Nursing Society

2 Objectives Name two possibilities for using information obtained through molecular profiling in the management of cancer. List two resources for increasing your knowledge base on cancer as a genetic disease and its implications for practice

3 Traditional Standards of Practice Histologic diagnosis Tumor cell morphology determines diagnosis Grading Staging Prognostic Indicators

4 Categorization of Cancer Diseases are generally lumped together Molecularly distinct disease are often lumped together in the same bucket Difficult to identify subclasses of like cancers

5 Stage 1 Breast Cancer 42 year old female diagnosed with 2.5 cm ductal carcinoma T2N0M0 Stage 1 Surgery and chemotherapy Multiple recurrences succumbs to disease within 5 years

6 Stage 1 Breast Cancer 58 year old female diagnosed with 2.5 cm ductal carcinoma T2N0M0 Stage 1 Surgery and chemotherapy Alive and NED ten years following diagnosis

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8 Traditional Knowledge Outside of age, both women presented with essentially the same disease By histology, grade, and stage there are no distinctions between the two Emerging prognostic indicators help guide decisions Current practice integrating the use of molecular signatures

9 Cancer has many faces under the microscope, however looks alone can only predict general categories of biological behavior. Liotta & Petricoin, Nature Oct 2000

10 Cancer Pathophysiology Cell and its machinery hardware Genes directions for the working of the cell software Cancer disease of progressive genetic changes Intuitive sense that different genetic changes lead to different pathophysiology

11 Molecular Profiling Analyzes the signature of each individual s tumor Provides ability to cluster tumors by algorithms Transcends histologic type Leads to classes of tumors within a given histologic diagnosis

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13 Applications of Current Scientific Knowledge Insights into pathogenesis Cancer diagnosis and prediction of clinical outcome Identification of therapeutic targets

14 Systems Medicine Systems medicine the application of the strategies, technologies and computational tools of systems biology to disease and wellness Systems approach essential for deciphering complexity

15 P4 Medicine P4 medicine the clinical applications of systems medicine to patients Predictive Preventive Personalized Participatory Hood, L & Flores M :N Biotechnol Mar 18

16 Cancer is a Disease of Genes Identification of high risk individuals Chemoprevention Early detection Prognosis New Targets

17 Why Pursue Testing? Perception of Risk Family Questions To Guide Treatment To Manage Risk

18 Current standards focus on lifestyle and environmental factors Identification of risk through specific genetic changes Cancer Prevention

19 Chemoprevention Coined by M. Sporn in the mid-1970s The pharmacologic inhibition of carcinogenesis or its reversal in premalignant stages Research focused on the use of the retinoids in UADT cancers Identification of biologic markers of intermediate end points

20 Chemoprevention: Targeted Diseases Colorectal Cancer Prostate Cancer Breast Cancer Bronchial dysplasia Second primary upper aerodigestive cancers Precancerous lesions Barrett s esophagus Modulation of biomarkers in precancerous breast lesions (e.g., LCIS) Dysplastic oral leukoplakia Cervical intraepithelial neoplasia (CIN) Bladder Cancer

21 Prognostics Prediction of response to therapy Guidance in selecting the appropriate types of therapy Segregation of Cancers

22 Oncotype DX Breast Cancer Assay for DCIS patients Predicts the risk of local recurrence (DCIS or invasive carcinoma) and predicts the risk of local invasive carcinoma. Helps guide personalized treatment based on tumor biology as determined by the DCIS Score.

23 Identification of Molecular Molecular mechanisms key to transformation Identification of new molecular targets for development of therapies Guidance of treatment choice Targets for Therapy

24 Monoclonal Antibodies as Target Therapy of Malignancy Approved Mabs Rituximab Trastuzumab Bevacizumab Cetuximab Panitumumab Ipilimumab

25 Anti-HER-2/neu MAB Transmembrane receptor that is overexpressed in 25%-30% of breast cancers Herceptin (Anti-HER-2/neu MAB) inhibits signal transduction and cell proliferation Activity as a single agent and in combination with traditional cytotoxic chemotherapy in metastatic BR CA

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27 Signal Transduction Modulators Imatinib Dasatinib Lapatinib Vemurafinib (BRAF v600e) Erlotinib Crizotinib Sunitinib Sorafenib Pazopanib

28 Advances in Lung Cancer EGFR receptor mutations Erlotinib Testing of second generation inhibitors ALK and EML-4 gene fusion Crizotinib Lung Cancer Mutation Consortium

29 INFORMATION Challenge For Molecular Therapeutics Understanding Of Cancer Translational Research Management Of Cancer Patients TIME

30 ..genetic discoveries will impact every nook and cranny of our practice Francis Collins, 1999

31 New Testing Technology DNA Chip Technology Evaluation of biomarkers - flags of disease

32 Bottlenecks Establishing the technology to support clinical practice and clinical research Ability to monitor in real time response to therapy Application to individual patients and subcategories of cancer N of one problem Increasing recognition of tumor complexity Ability to distinguish driver vs passenger mutations Mills & Baselga (2012) ASCO Post

33 The Nurse of the Future Has a knowledge based practice Commits to lifelong learning Embraces and manages change Possess the flexibility to adapt to a rapidly changing environment Is open to new roles and responsibilities Exhibits professionalism and leadership

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35 Strategies Media College courses Educational websites Eurogene Professional conferences Journals Scientific American Journal of Nursing Scholarship Vol 43(4) Dec 2011

36 Summary Improved understanding of molecular biology translated to disease at the molecular level Cancer conceptualized more as a chronic disease Advent of more oral therapies Pre-screening of therapies Ability to integrate information management technology into practice