Introduction
Lecture Oncology I
Prof. Dr. Susanne Sebens
2 Lecture Oncology I WS 2019/2020
| Susanne Sebens 21.10.2019
Lecture Oncology I is part of
focus area oncology (master program Medical Life Sciences)
module medoncol-01 (master programs Biology/Biochemistry)
certificate study program oncology (study program human medicine)
11 lectures covering basic and translational research as well as diagnostics and
therapy
Special lectures will be given by appropriate experts in the field.
Lecturers are not obligated to provide their lectures online.
Lecture plan/Lectures are provided online on http://www.medlife.uni-kiel.de (MLS
students), http://www.iet.uni-kiel.de/de/lehre or OpenOLAT
Written examen (applies to MLS and medical students):
10.02.2020 (30.03.2020), 10.30-12.00 a.m.
Language : English
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Applies to students of the master program Medical Life Sciences (Focus Area
Oncology):
This semester:
Lecture Oncology I; WS, monday 2.00-3.30 p.m. (+ written examen)
Seminar Oncology I (WS, monday, 3.45-4.30 p.m.; 1. seminar: 28.10.2019):
Publication corresponding to the topic of the lecture will be prepared and
discussed by all students (content and quality)
Publications will be provided one week in advance online on
http://www.medlife.uni-kiel.de
Laboratory weeks: 17.02.-28.02.2020 (Hospitation of different labs will be
organized)
Hospitation week: 02.03.-06.03.2020 (Clinical hospitation is organized)
Language: english, except: hospitation week
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Applies to students of the master program Medical Life Sciences (Focus Area
Oncology):
Next semesters:
Joint/Individual Seminar: SS2020, Friday
Project thesis: SS2020, 3 weeks experimental work + project thesis + oral presentation
Master thesis: WS2020/2021
Absence times: max. 14% (see FPO)
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Applies to students of the certificate study program oncology (study program
human medicine)
This semester:
Lecture Oncology I; WS, monday 2.00-3.30 p.m.
(+ written examen)
Seminar Oncology I (WS, monday, 3.45-4.30 p.m.):
1. seminar today: Writing scientific english
All other seminars: Publication corresponding to the topic of the lecture
Papers will be prepared and discussed by all students (content and quality)
Publications will be provided one week in advance online on http://www.iet.uni-
kiel.de/de/lehre and OpenOLAT
Lecture + Course Pathology (+ written exam)
Language: Lecture + Seminar Oncology > english
Lecture + Course Pathology > german
Absence times in seminar oncology: max. 14% (see FPO Medical Life Sciences)
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Applies to students of master programs biology/biochemistry
(Vertiefungsspezifisches Wahlpflichtfach)
Name/number of the module (15 credit points)
Molekulare Onkologie I (med-oncol01)
Mandatory attendance:
Lecture Oncology I; WS, monday 2.00-3.30 p.m.
Seminar Molekulare Onkologie + paper discussion; SS, friday 8.30-10.00 a.m.
Seminar Experimentelle Tumorforschung + oral presentation; SS and WS, thursday
3.30-4.30 p.m. (this WS 11 seminars )
or alternatively KON-Seminar; WS and SS, tuesday 5.00-6.00 p.m.
Internship: 3 weeks in the lab of one of the contibuting lecturers + protocol
Language: all lectures an seminars > english
Graded examination: Paper discussion in the seminar Molekulare Onkologie (50%)
+ lab protocol (50%)
Absence times: max. 40% (see respective FPO)
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Lecture & seminar Oncology I Lecture and Seminar: IET- seminar room , building U30, 3rd floor, R317
(Lecture: MLS, medoncol-01, certificate study program oncology; seminar: MLS + certificate study program oncology)
Dates of presentation Topic Lecturer Lecture: 21.10.2019, 14:00-15:30 Seminar: 21.10.2019 15.45-16.30
Introductory lecture Seminar: Scientific writing (only for certificate study program oncology)
Susanne Sebens; Institut für Experimentelle Tumorforschung
Lecture: 28.10.2019, 14:00-15:30 Seminar: 28.10.2019, 15:45-16:30
Causes of tumor formation Eva Murga; Institut für Humangenetik
Lecture: 04.11.2019, 14.00-15:30 Seminar: 04.11.2019, 15:45-16:30
Hallmarks of cancer: Genetics and Epigenetics Eva Murga; Institut für Humangenetik
Lecture: 11.11.2019, 14:00-15:30 Seminar: 11.11.2019, 15:45-16:30
Hallmarks of cancer: Sustained proliferation, evading growth suppressors, replicative immortality
Norbert Arnold; Klinik für Gynäkologie und Institut für Klinische Molekularbiologie
Lecture: 18.11.2019, 14:00-15:30 Seminar: 18.11.2019, 15:45-16:30
Hallmarks of cancer: Metabolic reprogramming Heiner Schäfer; Institut für Experimentelle Tumorforschung
Lecture: 25.11.2019, 14:00-15:30 Seminar: 25.11.2019, 15:45-16:30
Hallmarks of Cancer: Immune evasion and tumor promoting inflammation
Susanne Sebens; Institut für Experimentelle Tumorforschung
Lecture: 02.12.2019, 14:00-15:30 Seminar: 02.12.2019, 15:45-16:30
Hallmarks of Cancer: Malignant Progression (angiogenesis, invasion, metastastis, stemness)
Susanne Sebens; Institut für Experimentelle Tumorforschung
Lecture: 09.12.2019, 14:00-15:30 Seminar: 09.12.2019, 15:45-16:30
Hallmarks of cancer: Resistance to cell death (types of cell death and resistance mechanisms)
Anna Trauzold; Institut für Experimentelle Tumorforschung
Lecture: 16.12.2019, 14:00-15:30 Seminar: 16.12.2019, 15:45-16:30
Biomarker for personalized medicine (biomarker, biobanking, diganostic, ethics)
Christian Röder; Institut für Experimentelle Tumorforschung
Lecture: 13.01.2020, 14:00-15:30 Seminar: 13.01.2020, 15:45-16:30
Molecular imaging/diagnostics in oncology Sanjay Tiwari; Klinik für Radiologie/MOIN-CC
Lecture: 20.01.2020, 14:00-15:30 Seminar: 20.01.2020, 15:45-16:30
Oncological therapies I (conventional ) Lars Fransecky; Klinik für Innere Medizin II mit den Schwerpunkten Hämatologie und Onkologie
Lecture: 29.01.2020, 14:00-15:30 Seminar: 29.01.2020, 15:45-16:30
Oncological therapies II (biologicals + immuno therapy) Matthias Peipp; Sektion für Stammzelltransplantation und Immuntherapie
10.02.2020, 10:30-12:00 Written exam examination period 1 (MLS and certificate study program oncology)
Sebens
30.03.2020, 10:30-12:00 Written exam examination period 1 (MLS and certificate study program oncology)
N.N.
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deFacto Onkologie -Seminar
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In case of questions/problems….
please contact the lecturers or me
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Introduction
Lecture Oncology
1. General introduction into the topic
2. General introduction into the terminology
3. Position of the special lectures in the context of oncology
Aims of this lecture
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Cancer
What is cancer? What is a tumor? What is a neoplasm?
Tumor
> abnormal mass of tissue or cells resulting from deregulated cell growth (enhanced
proliferation and/or decreased apoptosis/cell death)
> Benign neoplasm: local disease, non-invasive, no formation of metastases
> Malignant neoplasm: progressive and invasive disease , infiltration of the surrounding
tissue +/- metastases
> Origin: almost every tissue/cell in the body
> Every swelling in the body caused by inflammation, infection, trauma....
> The term is commonly used as a synonym for cancer and neoplasm.
Neoplasm/Neoplasia
Medical term describing a class of diseases being characterized by an uncontrolled
/excessive expansion of cells/tissues.
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from: The Biology of Cancer (© Garland Science 2007)
Neoplasia can arise from different cells/tissues
Epithelial tissue
Tissue/cells of Origin > Cancer
Non-epithelial tissues
Central/Peripheral nervous system
Mesenchymal cells
Hematopoietic cells (blood cells)
Neuroectodermal tumors (~ 1% of all
cancers) e.g. glioblastoma
Sarcomas (~ 1% of all cancers)
Leukemia, Lymphoma (~ 6 % of all cancers)
Carcinoma (~ 80% of all cancers)
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From: Cancer Statistics 2018 Siegel et al.
Cancer diseases in the United States
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The hallmarks of cancer
Hanahan & Weinberg, Cell 2011 Enabling characteristics
> acquired functional capabilities that allow cancer growth and progression
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Risk factors - Genetics
~ 10 % of all cancers are related to a genetic predisposition
adapted from Cancer Research UK
Principal tumours Gene Penetrance (by age 70) Breast, ovarian,
bowel, prostate
BRCA1 Breast cancer approx
65-85%
Ovarian cancer approx
39-45%
Breast (including
male), ovarian
(lower than
BRCA1), prostate,
pancreatic
BRCA2 Female breast cancer
approx 45-80%
Male breast cancer 5%
Prostate cancer
approx 7.5%
• Cancer is a an age-related disease.
• Risk factors are still insufficiently understood for certain cancer diseases.
• Individual causes for every cancer disease and every individuum.
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Risk factors – Life Style
Avoidable !!!
• Smoking (~25/30% of all cancers)
• Nutrition (~ 9 %)
• Overweight/Obesity (~ 6 %)
• Alcohol (~ 4 %)
• Sun exposition
• Chemicals & radiation (asbestos, benzole, radioactivity, x-ray….)
• Hormones
• Chronic infections (HPV, HCV; H. Pylori) (~ 20 %)
Lecture/Seminar: 28.10.2019- Causes of tumor formation (PD Dr. Murga)
~ 90% of cancers are sporadic and promoted by exogenous/environmental factors
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Carcinogenesis (manifestation, development and progression)
Cancer is a polygenetic disease characterized by
an increasing number of mutations acquired within years/decades
„M
alig
nan
cy“
time
deregulated genes
• growth factors and/or their receptors
• regulators of cell death/apoptosis
• regulators of cell division/proliferation
• DNA-repair genes
• transcription factors
>>oncogenes/tumor suppressor genes
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Oncogene and tumor suppressor gene
Proto-Oncogene/Oncogene
Tumor suppressor gene
adapted from: The Biology of Cancer (© Garland Science 2007)
Proto-oncogenes encode for proteins regulating cell cycle progression and cell growth.
An oncogene becomes consitutively activated due to mutation.
Examples: Ras, Myc, Wnt
Tumor suppressor genes encode for proteins regulating cell cycle progression,
apoptosis and DNA-repair.
A tumor suppressor gene becomes partially or completely inactivated (by genetic or
epigenetic alteration).
Examples: p53, BRCA1+2, INK4a/p16
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Control and collaboration of cancer-associated genes
and their impact on cellular behavior
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from: Dr. Mark Hill
There is more than genetic... epigenetic and tumor progression
Changes in gene function due to an altered accessibility of the DNA/gene
transcription but not alteration of the DNA sequence (mutation)
DNA-Methylation:
addition of a methyl group to CpG islands
DNA-Methylation is common in tumors
> reduction of gene expression
Histone modifications:
e.g. methylation, acetylation, phosphorylation
Histone-deacetylation is common in tumors
> reduction of gene expression
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Summary I:
Carcinogenesis is driven by a deregulated gene expression
caused by
Lectures/Seminars
04.11.2019 - Hallmarks of Cancer: Genetics & Epigenetics (PD Dr. Murga)
11.11.2019 - Hallmarks of Cancer: Proliferation/ Growth suppression/Immortality
(Prof. Arnold)
09.12.2019 - Hallmarks of Cancer: Resistance to cell death (Prof. Trauzold)
Genetic alterations (mutations, chromosomal gains, losses, fusions)
Epigenetic modifications
Activation of oncogenes
Inactivation of tumor suppressor genes
Altered signal transduction
deregulated proliferation and cell death
increased survival of transformed cells
abnormal mass of cells/tissues
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Warburg-Effect Normal Metabolism
(Vander Heiden et al. Science 2009)
(Doherty JR, Cleveland JR ; JCI 2013)
Malignancy
(cell proliferation, apoptosis resistance, invasion)
Metabolic symbiosis
Metabolic reprogramming in tumorigenesis
Lecture/Seminar:
18.11.2019 –
Hallmarks of Cancer:
Metabolic Reprogramming
(Prof. Schäfer)
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Tumors comprise not only tumor cells
but also an inflammatory microenvironment Mamma carcinoma
Hodgkin´s lymphoma
from: The Biology of Cancer (© Garland Science 2007)
The tumor/inflammatory stroma defines the
non-neoplastic tissue within a tumor
1. non-cellular compartment
extracellular matrix (e.g. collagen, fibronectin, laminin)
chemokines, growth factors, proteases…
2. cellular compartment
endothelial cells
fibroblasts + activated fibroblasts
(=myofibroblasts/CAFs)
immune cells
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Cancer immunoediting:
From cancer control by the immune system
to immune evasion by cancer cells
(Modified from Veseyl et al,
Annu Rev immunol 2011)
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= Malignant transformation of cells leading to their spreading in the organism and
formation of metastases
Malignant progression is…
(Fidler IJ. Nat. Rev. Cancer 2002 + The Biology of
Cancer (© Garland Science 2014)
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When does metastasis start?
(C.A. Klein Cell Cycle 2004; C.A. Klein Nature 2009)
linear
parallel
linear
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Which cells are responsible for tumor initiation at primary
and secondary sites? Cancer stem cell theory
Definition (AACR workshop on cancer stem cells 2006):
„ a cell within a tumor that possess[es] the capacity to self-renew
and to cause the heterogenous lineages of cancer cells“
Fulawka et al. Bio. Res. 2014
differentiation Self-renewal
Stem cell properties can be gained & lost
(O`Connor et al. , Cancer Letters 2014)
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Development and progression of tumors are promoted by
an inflammatory microenvironment
loss of immune control and immune evasion of the tumor cells
angiogenesis
acquisition of an invasive phenotype and high cellular plasticity
cancer stem cell properties
(early) dissemination and colonization in secondary organs
outgrowth and formation of metastastes
Lectures/Seminars:
25.11.2019 – Hallmarks of Cancer: Immune evasion & Inflammation (Prof. Sebens)
02.12.2019 – Hallmarks of Cancer: Malignant progression (angiogenesis, invasion,
dormancy, cancer stemness) ( Prof. Sebens)
Summary II:
Inflammation & malignant progression in carcinogenesis
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Cancer research is mandatory to improve treatment of cancer patients
pre
ven
tio
n
dia
gn
osti
cs
thera
py
Successful treatment
of cancer patients
psychological
support
nutrition physical
activity
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Prevention aims at avoiding the onset of tumor develoment
> Avoiding of exposition to carcinogens > Regular screenings
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Sensitive and specific differentiation
between non-neoplastic and neoplastic cells/tissues
Diagnostics
Diagnosis of neoplasia at early stages commonly allow curative treatment!
Suitable imaging modalities
Current problem: do commonly not detect
small lesions/precursor lesions
Need for sensitive & specific markers > biomarkers
(tissue, serum, other liquid biopsies)
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Use of biomarkers at different stages in clinical evolution of cancer
(Ludwig & Weinstein, Nature Reviews Cancer 2005)
Lectures/Seminars:
16.12.2019 - Biomarker for personalized medicine (Dr. Röder)
13.01.2020 - Molecular Imaging & Diagnostics (Dr. Tiwari)
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Oncological therapies
Surgery
Chemotherapy
Radiotherapy
Hormone therapy
Biologicals (antibodies, small molecule inhibitors…)
Immunotherapy
Strategies to specifically target tumor cells
Strategies to specifically target stromal cells and their tumor promoting factors
Combinations of different therapeutic strategies
Stratification of patients (usage of biomarkers)
> > > „Personalized/individualized“ medicine
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Summary III: Diagnostics and therapy of cancer
The detection of a neoplasm in early stages often leads to cure of the disease.
Biomarker become more and more important for prevention, diagnosis and
treatment of cancer diseases.
Cancer therapies have become very complex and precise (targeted
therapies/personlized therapies).
Lectures/Seminars:
20.01.2020 - Oncological Therapies (conventional) (Dr. Fransecky)
27.01.2020 - Oncological Therapies (biologicals/immunotherapy)
(Prof. Valerius/Prof. Peipp)
Examination (Medical Life Sciences+ certificate study program oncology):
10.02.2020 (30.03.2020)
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The Biology of Cancer
Author: Robert A. Weinberg
Publisher: Garland Science Taylor & Francis Group
Molecular Biology of Cancer
Author: Lauren Pecorino
Publisher: Oxford University Press
German:
Molekulare Onkologie – Entstehung, Progression, klinische Aspekte
Autor: Christoph Wagener & Oliver Müller
Verlag: Thieme
Recommended literature
Review