Patología molecular desde la territorial madrileña. Innovation Unit HCSC/Pathological Anatomy Unit/Diagnostic Imaging Service/

Transcripción

1 Patología molecular desde la territorial madrileña Innovation Unit HCSC/Pathological Anatomy Unit/Diagnostic Imaging Service/ December 2011

2 Management of cabcer (i.e.nsclc) today Analysis Treatment CPNM Staging Early stage Advanced stage surgery Tissue Subtype Histological 80-85%? Adjuvant (CT; RT) Genotypo 15-20% Targeted therapy

3 PET ( )

4 Circuito de derivaciones. Red inter-hospitalaria. Circuito de consultoría, segunda opinión y apoyo en calidad. Formación continuada: De técnicos y biólogos De residentes. Patólogos generales Patólogos especializados en patología molecular Red detelepatología Grupo asesor de la territorial 3-5 expertos y Presidente. Apoyo a plataformas Programa teórico: 2-3 convocatorias en distintos lugares Programa práctico: Hasta 10 centros Acreditación, certificación 4

5 Types of biomarkers associated with targeted therapies. Histopathological subtype (I.E: Pemetrexed, avastin). Non responder Immunohistochemistry (HER2, c-met, EGFR ) FISH: HER2, ALK... Algorithms PCR: gene mutations: K-ras, EGFR,c-kit... Responder Others

6 QAP at SEAP: HER2-neu Results

7

8 Opportunity Biomarkers predictive for targeted therapy reponse need to be improved. Difficulties and limitations of molecular biomarkers assesment. Lack of reproducibility between centers (10-20% discordance rates) Need of optimal distribution of the tissue for pathology, IHC, FISH or PCR, especially in small biopsy or cytology Histopathology (fixation, tumor cells rate, necrosis..) is crucial for quality assurance of any biomarker Different technical options to choose, even IHC vs FISH vs PCR.

9

10 Signal transduction inhibitors: FDA or AEM-approved therapies Imatinib mesylate (Gleevec ) sm approved to treat GIST,certain kinds of leukemia, dermatofibrosarcoma protuberans, myelodysplastic/myeloproliferative disorders, and systemic mastocytosis. Dasatinib (Sprycel ) CML or acute lymphoblastic leukemia. The drug is a smallmolecule inhibitor of several tyrosine kinase enzymes. Nilotinib (Tasigna ) CML. The drug is another small-molecule tyrosine kinase inhibitor. monoclonal Antibody (mab) Trastuzumab (Herceptin ) mab is approved for the treatment of certain types of breast cancer as well as some types of gastric or gastroesophageal junction adenocarcinoma. Trastuzumab may as well,induce the immune system to attack cells that express high levels of HER-2. Lapatinib (Tykerb ) s-m for advanced or metastatic breast cancer. HER-2. Small-molecule (S-m)

11 Gefitinib (Iressa ) is approved to treat patients with advanced non-small cell lung cancer. Erlotinib (Tarceva ) is approved to treat metastatic non-small cell lung cancer and pancreatic cancer that cannot be removed by surgery or has metastasized. This small-molecule drug inhibits the tyrosine kinase activity of EGFR. Cetuximab (Erbitux ) is a mab, squamous cell carcinoma of the head and neck or colorectal cancer.. Panitumumab (Vectibix ) is mab for metastatic colon cancer. Temsirolimus (Torisel ) is approved to treat patients with advanced renal cell carcinoma. This smallmolecule drug is a specific inhibitor of a serine/threonine kinase called mtor that is activated in tumor cells and stimulates their growth and proliferation. Everolimus (Afinitor ) is approved to treat patients with advanced kidney cancer whose disease has progressed after treatment with other therapies. This small-molecule drug binds to a protein called immunophilin FK binding protein-12, forming a complex that in turn binds to and inhibits the mtor kinase. Vandetanib (Zactima ) is approved to treat patients with metastatic medullary thyroid cancer who are ineligible for surgery. This small-molecule drug binds to and blocks the growth-promoting activity of several tyrosine kinase enzymes, including EGFR, several receptors for vascular endothelial growth factor receptor (VEGF), and RET. Vemurafenib (Zelboraf ) inoperable or metastatic melanoma. This small-molecule drug blocks the activity of a permanently activated mutant form of the serine/threonine kinase BRAF (known as BRAF V600E). Crizotinib (Xalkori ) locally advanced or metastatic non-small cell lung cancer. EML4-ALK,

12 Angiogenesis: Bevacizumab (Avastin ) mab for glioblastoma, NSCLC, metastatic breast cancer, metastatic colorectal cancer, and metastatic kidney cancer. Binds to VEGF Sorafenib (Nexavar ) renal cell carcinoma and some cases of hepatocellular carcinoma. One of the kinases that sorafenib inhibits is involved in the signaling pathway that is initiated when VEGF binds to its receptors. Sunitinib (Sutent ) is another small-molecule tyrosine kinase inhibitor that is approved for the treatment of patients with metastatic renal cell carcinoma, GIST that is not responding to imatinib, or pancreatic neuroendocrine tumors that cannot be removed by surgery, are locally advanced, or have metastasized. Pazopanib (Votrient ) advanced renal cell carcinoma. Pazopanib is a small-molecule inhibitor of several tyrosine kinases, including VEGF receptors, c-kit, and platelet-derived growth factor receptor. Targeted therapies helping the immune system to destroy cancer cells: Rituximab (Rituxan ) mab for certain types of B-cell non-hodgkin lymphoma and, when combined with other drugs, to treat chronic lymphocytic leukemia (CLL). The therapy recognizes CD20 Alemtuzumab (Campath ) B-cell CLL. mab against CD52. Binding of alemtuzumab to CD52 triggers an immune response that destroys the cells. Ipilimumab (Yervoy ) unresectable or metastatic melanoma.

13 How can we improve molecular biomarkers for targeted therapy? Consensus guidelines Automation Integration Tissue evaluation and handling Continued education QAP and accreditation

14 Automation of: Pre analytical phase Analytical phase: real time PCR, IHC, FISH, CISH, SISH. Interpretation Quantyfication and evaluation of IHC and /or FISH Expert software integrated with scanning systems for morphology, IHC, CISH SISH or FISH

15 Workflow: fácil, rápido y fiable

16 Encuentro para la investigación, divulgación científica y foros de debate sobre biomarcadores predictivos. Qué puedes encontrar?: Análisis Bibliográficos Rss Feed de revistas científicas Banco de imágenes Protocolos de calidad Eventos destacados Documentos de interés - Consensos SEOM-SEAP Formación, Educación y Charlas Online SEOM-SEAP Consenso HER2 CM Consenso HER2 CG Consenso CPCNP

17 Qué puedes encontrar?: CURSOS INTERACTIVOS: Casos reales con un tutor personal. Zoom de imágenes. Respuestas comentadas por expertos. PREGUNTE AL EXPERTO: Panel de profesionales y expertos responderán a sus preguntas y dudas.

18 Visualización, sistemas expertos Virtuoso (ROCHE) NEC Philips epathologists cancer diagnosis assistence system Leica Ariol Review and Slidepath gateaway Vitropath Aurora Interactive mscope education suite Problemas Precio, desenfoques, planos superpuestos, interfaces, formato ficheros, interpolación Nuevas modalidades Imagen multiespectral Microscopía confocal, ecoendoscopia

19 Escáner para campo claro (IHC, SISH, CISH) o fluorescencia (FISH) Fases Digitalización Almacenamiento Visualización Rapidez y calidad de imagen A 40x, eje Z, 0.25 um por pixel Ejemplos Aperio ScanScope CC, F Leica SCN 400F, CC, F 3DHistotech CC, F Roche Ventana iscan HT CC Hamamatsu CC, F Menarini Dsight y SightFluo CC, F Philips slide scanner GE Omnyx VL120 UNIC technologies, Motic (China) Usos Asistencial: DIAGNOSTICO REGISTRO DE TUMORES AHORRO PRUEBAS REPETIDAS Consulta/ 2ª opinión Docencia/Sesiones

20 Desarrollar un sistema que permita el apoyo a la decisión sobre el diagnóstico de cáncer en muestras de tejidos Específicos: de investigación Muestras Aprendizaje Escaneado Red madrileña por subespecialidades Coordinador Apoyo al Diagnóstico Almacenamiento PACS Sistema Experto Consultores Otros Afines Consulta 20

21 The Team People:, roles, responsabilities 21