Diagnostic technology has improved Past- Macro/Micro Level Tests differentiated disease from 25736 non-disease Disease defined by location, size F/- and morphology Today - Molecular Level f Disease defined by individual biology and / or dNa of tumor Tests to subcategorize disease: predict outcomes of specific therapeutic screen for adverse events monitor disease
Past – Macro/Micro Level • Tests differentiated disease from non-disease • Disease defined by location, size and morphology Today – Molecular Level • Disease defined by individual biology and /or DNA of tumor • Tests to subcategorize disease: • predict outcomes of specific therapeutic • screen for adverse events • monitor disease Diagnostic technology has improved
Cancer is experiencing a shift toward precision medicine 5 Year Years Ago Hematologic oncology Survival Years Ago “ Disease of the blood 0% Leukemia or Lymphoma Years Ago Chronic leukemia Indolent Lymphoma Acute Leukemia Aggressive Lymphoma 38 Leukemia types identified Acute myeloid leukemia(12 types) Mature B-cell lymphomas (-14 types) Today Acute lymphoblastic leukemia(2 types Mature T-cell lymphomas(15 types) Acute promyelocytic leukemia(2 types Plasma cell neoplasm( 3 types) Acute monocytic leukemia(2 types Immature(precursor) lymphomas(2 types Acute erythroid leukemia(2 types) Hodgkin's lymphoma (5 types Acute megakaryoblastic leukemia Immunodeficiency associated lymphomas(5 types) Acute myelomonocytic leukemia(2 types Other hematolymphoid neoplasms(-7 types Chronic myeloid leukemia Chronic myeloproliferative disorders(5 types) Myelodysplastic syndromes (6 types) Mixed myeloproliferative/myelodysplastic syndromes (3 types 70% Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2002, National Cancer Institute.BethesdamD,http.://seer.cancergovlcsr/19752002/,basedonNov2004Seerdatasubmissionpostedto the seer web site 2005
Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2002, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2002/, based on Nov 2004 SEER data submission, posted to the SEER web site 2005. 80 Years Ago 60 Leukemia or Lymphoma Years Ago Chronic Leukemia Acute Leukemia Preleukemia Indolent Lymphoma Aggressive Lymphoma 100 Years Ago “Disease of the Blood” Today ∼38 Leukemia types identified: Acute myeloid leukemia (∼12 types) Acute lymphoblastic leukemia (2 types) Acute promyelocytic leukemia (2 types) Acute monocytic leukemia (2 types) Acute erythroid leukemia (2 types) Acute megakaryoblastic leukemia Acute myelomonocytic leukemia (2 types) Chronic myeloid leukemia Chronic myeloproliferative disorders (5 types) Myelodysplastic syndromes (6 types) Mixed myeloproliferative/myelodysplastic syndromes (3 types) ∼51 Lymphomas identified: Mature B-cell lymphomas (∼14 types) Mature T-cell lymphomas (15 types) Plasma cell neoplasm (3 types) Immature (precursor) lymphomas (2 types) Hodgkin’s lymphoma (5 types) Immunodeficiency associated lymphomas (∼5 types) Other hematolymphoid neoplasms (∼7 types) 5 Year Survival ~ 0% 70% Hematologic oncology Cancer is experiencing a shift toward precision medicine
Common gene variations Oncogene a gene with the potential to cause cancer often mutated or expressed at high levels in tumor cells Proto-oncogene a normal gene that can become an oncogene due to mutations or increased expression coding for proteins that help to regulate cell growth and differentiation anti-oncogene, or tumor suppressor gene a gene protecting a cell from one step on the path to cancer When mutated to cause a loss or reduction in its function the cell can progress to cancer in combination with other genetic changes
Common gene variations Oncogene • a gene with the potential to cause cancer • often mutated or expressed at high levels in tumor cells Proto-oncogene • a normal gene that can become an oncogene due to mutations or increased expression • coding for proteins that help to regulate cell growth and differentiation anti-oncogene, or tumor suppressor gene • a gene protecting a cell from one step on the path to cancer • when mutated to cause a loss or reduction in its function, the cell can progress to cancer in combination with other genetic changes
Dominant Oncogenes Identified as transforming genes in viruses with functions as. Products involved in: cell cycle/cell division /differentiation Control of normal cellular growth differentiation mediated by growth Factors growth Factor Receptors cytokines Intracellular pathways activated Activation Repression of various genes
Dominant Oncogenes Identified as transforming genes in viruses with functions as: • Products involved in: cell cycle / cell division / differentiation • Control of normal cellular growth & differentiation mediated by: – growth Factors – growth Factor Receptors – cytokines • Intracellular pathways activated • Activation / Repression of various genes
Examples of Oncogenes abl CML translocation bcl2 Follicular Lymphoma translocation erbB-2 Breast/ovarian carcinoma amplification c-myc Burkitt's lymphoma translocation ras Thyroid/Colon carcinoma point mutation ret Thyroid carcinoma ent rearrangement
Examples of Oncogenes abl CML translocation bcl2 Follicular Lymphoma translocation erbB-2 Breast/ovarian carcinoma amplification c-myc Burkitt’s lymphoma translocation ras Thyroid /Colon carcinoma point mutation ret Thyroid carcinoma rearrangement