The 1971 War on Cancer Revisited
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1 The 1971 War on Cancer Revisited Authors: Roland Mertelsmann Submitted: 2. November 2016 Published: 5. November 2016 Volume: 3 Issue: 6 Keywords: cancer, evolution, bioethics, symposium DOI: /josha Journal of Science, Humanities and Arts josha.org JOSHA is a service that helps scholars, researchers, and students discover, use, and build upon a wide range of content
2 THE 1971 WAR ON CANCER REVISITED Symposium Science, Ethics and Arts October 14, 2016 Prof. em. Dr. Drs. h.c. Roland Mertelsmann Department of Medicine I, Hematology, Oncology, Stem Cell Transplantation Freiburg University Medical Center International Master Program of Biomedical Sciences (IMBS) BIOTHERA-Foundation JOSHA Journal of Science, Humanities and Arts
3 THE WAR ON CANCER Continues 2016 For the loved ones we`ve all lost, for the families that we can still save, let`s make America the country that cures cancer once and for all President Barack Obama, State of the Union Address, Jan 12, 2016 Aiming High Changing the Trajectory for Cancer Lowy & Collins, NEJM April 2016
4 Cancer: The Emperor of All Maladies? 3
5 Oncogenesis Increasing autonomy, genetic instability and... L. Luzzatto, P.P. Pandolfi, NEJM 373, 84, 2015
6 Oncogenesis...Clonal Evolution L. Luzzatto, P.P. Pandolfi, NEJM 373, 84, 2015
7 Evolution and Cancer Priciples of Evolution 1. Mutations by Chance, limited by possible options 2. Opportunity: Survival advantage under the given conditions 3. Selection of the fittest Cancer Cells Acquire Immortality Increasing loss of controls driven by entropy
8 Oncogenesis: Conclusion Cancer is an aquired genetic disease Cancer is the continued evolution of cells within an individuum Oncogenesis and the clinical disease follow the Darwinian principles of evolution Genetic and epigenetic factors contribute to carcinogenesis and evolution Mutated genes/proteins may serve as molecular targets for small molecules, antibodies, CART cells as (neo)antigens for immune system recognition/attack Pathophysiological hallmarks identify potential therapeutic pathways
9 Targeted Therapies Small (designer) molecules Some Leukemiascan nowbe cured Good results also in some solid tumors Monoclonal Antibodies Lymphoma, Leukemia: significantly improved survival Lung cancer, colon cancer, others Transgenic T Cells (CART Cells) Highly active in leukemias In preclinical models also in solid tumors
10 Harnessing the Immune System 1. non-specific defense mechanisms 2. Immunisation, Prophylactic - Therapeutic: e.g. HPV 3. Liberating endogenous immunity: Immune Checkpoint Inhibition
11 Clonal Evolution: The Hydra Challenge
12 Genetic Evolution - Clonal Evolution Clonal evolution in cancer, M. Greaves, C.C. Maley, Nature 481, , 2012
13 Clonal Evolution Nature Jan 11; 481(7382):
14 Cancers are different from Patient to Patient within one Patient over Time Individualized/Personalized Evidence- Based Therapy Humans differ in their genetic program in comorbidities in their values, dreams and priorities Variability Necessitates Individual Therapeutic Strategies 1
15 Precision Medicine Bringing it to the Patient What is precise for the Individual? The Old Model 1. Phase I, II, III Studies in large, higly selected cohorts of patients aiming for improved response rates 2. Standard of Care in Guidelines for unselected patients focussed on clinical/pathological cancer type and stage The New Model Studies in small cohorts aiming for high response rates focussed on Molecular Signature of Cancer The Innovation Pathway Focussed on the optimal therapeutic strategy for the Individual Patient Based on all available evidence And careful risk benefit analysis
16 The 1971 War on Cancer Revisited Reconnaisance Understanding cancer: Oncogenesis and Clonal Evolution 2. Identify Therapeutic Targets Cancer Pathways, molecular and metabolic Cancer Molecules 3. Strengthen the Defenses Activate the immune system 4. My Strategy for "Winning the War Develop the innovation pathway PEBM Identify novel therapeutic objectives; stable disease vs. Remission Evaluate guidelines and Tumor Boards as management standard In silico experiments, modeling, simulation: Artificial intelligence Search for missing links, Phenotype genotype fallacy
17 Carcinogenesis: Simulations and Machine Learning The virtual experiment: Ø 10 variables Ø With 5 concentrations Ø At 10 timepoints Ø 10e50 possibilities Task: adjust input buttons to provide maximum number of cells 1. In virtual Petri dish 2. In output (Metastases) manual Program simulations machinelearning 1050 experiments, 175 combinations x 6 runs
18 "Mitosis" Computer Game "Real Time Evolution Simulation and Imaging"
19 2015: 10 Rules to Prevent Cancer 1. Do not smoke. 2. Do not smoke. 3. Do not smoke. 4. Avoid carcinogens: Asbestos, UV-Light, Aflatoxine. 5. Diet: moderate in calories, salt, fat, little Alcohol x daily fresh fruit and vegetable. 7. Exercise and watch your weight. 8. Vaccination (Hepatitis B, HPV) and Treatment of chronic infections. 9. Good genes. 10. Good luck!! Paul Kleihues 2007
20 Oncology Still fighting Cancer Thank you to the Speakers and Audience! My Mentors My Colleagues My Mentees and Alumni Our Patients The Symposium Team Bärbel Schätzle Evgenia Alechine Stephan Seiler
21 Clonal Evolution: The Hydra Challenge Cassandra Willyard Cancer: An evolving threat Nature 532, 166, 2016 Tumours are subject to the same rules of natural selection asanyother living thing. CANCER IS CONTINUOUSLY ADAPTING, THEREFORE WE HAVE TO DO SO AS WELL.
22 Cancer: Evolution und Adaptation Survival of the fittest Genetic Evolution of DNA assures the longterm survival advantage of cancer cells Epigenetic Adaptation assures the rapid adaptation to the environment flexible Phenotype, e.g. MET Transition "Cancer is a moving target" Cancer Stem Cell a Mirage
23 Oncogenesis Factors in Oncogenesis 1. Chance 30%? 2. Other? Probability of Penetrance dependent on 1. Genetic Predisposition 2. Population Size 3. Proliferative Rate 4. Environmental Factors 5....
24 Harnessing the Immune System Immune Checkpoint Inhibition numerous positive clinical trials demonstrating high efficacy and long-lastin remissions in Melanoma, various ST, HD; others underinvestigation autoimmune side-effects
25 Oncology The War on Cancer Albert Einstein Everything should bemadeas simple as possible, but not simpler.
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