Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Cancer - Genome BC
Document related concepts
no text concepts found
Transcript
Cancer Unlocking a Genetically Driven Disease Joseph M Connors, MD British Columbia Cancer Agency University of British Columbia Centre for Lymphoid Cancer Vancouver, BC Cancer Noteworthy World Statistics 2012 • Incidence > 14,100,000 will rise to 24 million by 2030 • Deaths > 8,200,000 • Prevalence > 32,600,000 • • Leading cause of death in developed world 2nd leading cause of death in developing world • In the developed countries Approximately 1 in 2 will develop cancer and 1 in 4 will die from cancer • The developing countries are rapidly catching up Canadian Cancer Statistics 2014 Change in Death Rates by Cause 1950 - 2005 x 64% post 5% 74% 58% Non-Hodgkin Lymphoma Incidence by Age Zheng, Cancer, 1992;70:840 Absolute number of new cancer patients doubles every 15-20 y Time ---------->>>> Our bodies are composed of many hundreds of different types of cells all working together in cooperation. Tissues are composed of cells talking to each other Cancer What is it Fundamentally? 70,000,000,000,000 cells throughout the body 1,000,000,000,000 must be constantly replenished = cell proliferation Obsolete cells must be constantly removed = apoptosis (programmed cell death) There must be a master set of instructions Basic Gene Structure and Control Whole Gene Regulators Promoter Genetic Information Duplication = trisomy Deletion ? ? MFISH - complex karyotype 9 1 9 3 1 9 3 1 3 1 Cumulative genetic errors BCL2 overproduction Cumulative genetic errors X Cytotoxic T-cells attacking an infected cell Split-reads across the breakpoint Aligned paired-end sequences Double-hit for the microenvironment •Translocations or copy number increase in PDL2 and PD-L1 • Translocations of CIITA (38%) Steidl et al., Blood 118: 2659-69 (2011) Cancer is a Dance Between Malignant Cells and Immune Destroyer Cells IFNγ T-cell receptor IFNγR MHC PI3K NFκB Tumor cell Other PD-L1 Shp-2 Nivolumab PD-L2 T cell PD-1 PD-1 Brahmer et al N Engl J Med 2012;366:2455 Topalian et al N Engl J Med 2012;366:2443-54 Cancer: Basically a Genetic Disease • Cancer cells are genetically abnormal and unstable • Our ability to keep from developing cancer is genetically controlled • Best route forward to effective treatment = using genetic instructions to reprogram cancer cells and immune cells
