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December 2011 Innovation Unit HCSC/Pathological Anatomy Unit/Diagnostic Imaging Service/ Patología molecular desde la territorial madrileña
December 2011
Innovation Unit HCSC/Pathological Anatomy Unit/Diagnostic
Imaging Service/
Patología molecular desde la
territorial madrileña
Management of cabcer (i.e.NSCLC) today
Tissue
Genotypo
Staging
Subtype
Histological
surgery
Targeted
therapy
Adjuvant
(CT; RT)
“Early stage”
“Advanced stage”
?
CPNM
Analysis Treatment
80-85%
15-20%
PET (1-12-10)
• 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
Types of biomarkers associated with targeted therapies.
– Histopathological subtype (I.E: Pemetrexed, avastin).
– Immunohistochemistry (HER2, c-met, EGFR…)
– FISH: HER2, ALK....
– PCR: gene mutations: K-ras, EGFR,c-kit....
– Others
Algorithms
Non responder
Responder
QAP at SEAP: HER2-neu Results
2004-2010
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.
FDA or AEM-approved therapies
Signal transduction inhibitors:
• 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 small-molecule inhibitor of several tyrosine kinase enzymes.
• Nilotinib (Tasigna®) CML. The drug is another small-molecule tyrosine kinase inhibitor.
• 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.
monoclonal Antibody (mAb)
Small-molecule (S-m)
• 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 small-molecule 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,
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.
How can we improve molecular biomarkers for targeted
therapy?
• Consensus guidelines
• Automation
• Integration
• Tissue evaluation and handling
• Continued education
• QAP and accreditation
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
Encuentro para la investigación, divulgación científica y foros de debate
sobre biomarcadores predictivos.
www.dianasterapeuticas.com
¿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
Consenso HER2
CM
Consenso HER2
CG
Consenso CPCNP
Consenso CRC
SEOM-SEAP
www.her2testing.es
¿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.
• 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
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
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Desarrollar un sistema que permita el apoyo a la decisión sobre el diagnóstico de cáncer en muestras de tejidos
Específicos: de investigación
Muestras
Escaneado
Almacenamiento
PACS
Sistema Experto
Apoyo al Diagnóstico
Aprendizaje
Coordinador
Consultores
Afines
Otros
Consulta
Red madrileña por
subespecialidades
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The Team
• People:
• , roles, responsabilities
