Introduction Lecture Oncology I - Uni Kiel

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



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



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)



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)

http://www.iet.uni-kiel.de/de/lehre






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)



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


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)


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.





deFacto Onkologie -Seminar



In case of questions/problems….

please contact the lecturers or me



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



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.



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)



From: Cancer Statistics 2018 Siegel et al.

Cancer diseases in the United States



The hallmarks of cancer

Hanahan & Weinberg, Cell 2011 Enabling characteristics

> acquired functional capabilities that allow cancer growth and progression

https://antisensescienceblog.files.wordpress.com/2014/07/hallmarks-10.png



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.

http://www.google.de/imgres?imgurl=http://www.brighamandwomens.org/publicaffairs/Images/DNA_with_mutation.jpg&imgrefurl=http://picsdigger.com/keyword/dna mutation/&usg=__PPIiwyjN6cN-x7dwBAkptyDZXaA=&h=292&w=411&sz=69&hl=de&start=4&zoom=1&tbnid=csH32kx0I_PrnM:&tbnh=89&tbnw=125&prev=/images?q=DNA+mutation&hl=de&gbv=2&tbs=isch:1&itbs=1



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

http://www.google.de/imgres?imgurl=http://3.bp.blogspot.com/_cDz1Gn_mB80/R1GWEKnXhfI/AAAAAAAAA1s/IxUrmr4ML_4/s1600-R/Zwei_zigaretten.jpg&imgrefurl=http://vom-herrn.blogspot.com/2007/12/zwei-zigaretten.html&usg=__40PzpmnTOlHwis3KUJbN35TYOfQ=&h=480&w=524&sz=49&hl=de&start=3&zoom=1&tbnid=T_dRZJCx68lk6M:&tbnh=121&tbnw=132&prev=/images?q=zigaretten&hl=de&gbv=2&tbs=isch:1&itbs=1

http://www.google.de/imgres?imgurl=http://manfredthurm.files.wordpress.com/2008/06/alkohol1.jpg&imgrefurl=http://manfredthurm.wordpress.com/2008/06/24/alkohol/&usg=__zlv9vf9K2LeD7KPgx2E_XfVivi8=&h=465&w=620&sz=37&hl=de&start=1&zoom=1&tbnid=5yt4opI_4NnsbM:&tbnh=102&tbnw=136&prev=/images?q=alkohol&hl=de&sa=G&gbv=2&tbs=isch:1&itbs=1

http://www.google.de/imgres?imgurl=http://www.n24.de/media/import/dpainfoline/dpainfoline_20080831_16/uebergewicht_18810058originallarge-4-3-800-0-422-1921-1860.jpg&imgrefurl=http://www.n24.de/news/newsitem_3741924.html&usg=__XWV-DHnk2sMv3dYpdtDNVOHg1zM=&h=598&w=800&sz=46&hl=de&start=7&zoom=1&tbnid=j63p6ReBWMwoCM:&tbnh=107&tbnw=143&prev=/images?q=fettsucht&hl=de&gbv=2&tbs=isch:1&itbs=1

http://www.google.de/imgres?imgurl=http://www.blogatino.de/cmg/albums/userpics/10001/pralle_sonne_03_03_06.jpg&imgrefurl=http://blogatino.de/wpb/?m=20060303&usg=__gBqoHY7Ld95iK3E6KEjsaf8RA5E=&h=400&w=530&sz=23&hl=de&start=6&zoom=1&tbnid=bK1xdgOWEpoN1M:&tbnh=100&tbnw=132&prev=/images?q=sonne&hl=de&gbv=2&tbs=isch:1&itbs=1

http://www.google.de/imgres?imgurl=http://diepresse.com/images/uploads/9/d/3/350675/APDietherEndlicher20071227135950.jpg&imgrefurl=http://diepresse.com/home/panorama/350675/index.do?gal=350675&index=2&direct=&_vl_backlink=&popup=&usg=__ImadEkjOdl5Q5Z-tNEOUhuu7QrY=&h=425&w=320&sz=50&hl=de&start=4&zoom=1&tbnid=5U978WxsQzyw7M:&tbnh=126&tbnw=95&prev=/images?q=fettes+essen&hl=de&gbv=2&tbs=isch:1&itbs=1

http://www.google.de/imgres?imgurl=http://help-genitalwartstreatment.com/wp-content/uploads/2010/05/hpv-human-papillomavirus.jpg&imgrefurl=http://help-genitalwartstreatment.com/symptoms-of-hpv-human-papillomavirus&usg=__U6_hjEBorpBlRrLIhlLW0WkJuYQ=&h=300&w=300&sz=50&hl=de&start=30&zoom=1&tbnid=qhQUL73iG7IZaM:&tbnh=116&tbnw=116&prev=/images?q=HPV&start=20&hl=de&sa=N&gbv=2&tbs=isch:1&itbs=1

http://www.google.de/imgres?imgurl=http://www.physicsmasterclasses.org/exercises/bonn2/de/images/strahlen.jpg&imgrefurl=http://www.physicsmasterclasses.org/exercises/bonn2/de/inhalt-3.5.2.html&usg=__6dI5kqRcMGJBat5cRuQzSO1m81A=&h=384&w=384&sz=25&hl=de&start=9&zoom=1&tbnid=Pi98jAG3MKlyvM:&tbnh=123&tbnw=123&prev=/images?q=radioaktive+strahlung&hl=de&gbv=2&tbs=isch:1&itbs=1

http://www.google.de/imgres?imgurl=http://www.planet-wissen.de/natur_technik/anatomie_mensch/hormone/img/wf_verhuetung_pille_g.jpg&imgrefurl=http://www.planet-wissen.de/natur_technik/anatomie_mensch/hormone/wissensfrage_hormone.jsp&usg=__CG68aI7JB_hzSC3Zz4nDr0gnFKg=&h=300&w=450&sz=50&hl=de&start=8&zoom=1&tbnid=vKTQCTrvQXAWMM:&tbnh=85&tbnw=127&prev=/images?q=pille&hl=de&gbv=2&tbs=isch:1&itbs=1



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



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



Control and collaboration of cancer-associated genes

and their impact on cellular behavior



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



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



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)



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



Cancer immunoediting:

From cancer control by the immune system

to immune evasion by cancer cells

(Modified from Veseyl et al,

Annu Rev immunol 2011)



= 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)



When does metastasis start?

(C.A. Klein Cell Cycle 2004; C.A. Klein Nature 2009)

linear

parallel

linear



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)

http://onlinelibrary.wiley.com/doi/10.1002/ijc.27961/full



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



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



Prevention aims at avoiding the onset of tumor develoment

> Avoiding of exposition to carcinogens > Regular screenings

http://www.aerztezeitung.de/extras/fotos/?sid=540801&sh=0



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)



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)



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



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)



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

Documents

Introduction Lecture Oncology I - Uni Kiel