Oncology
Inhoudsopgave
LE introduction.......................................................................................................................................3
LE cancer epidemiology (Alina Vrieling)..................................................................................................3
Descriptive cancer epidemiology........................................................................................................3
Prevalence......................................................................................................................................3
Incidence........................................................................................................................................3
Mortality.........................................................................................................................................4
Relative survival..............................................................................................................................4
Etiology...............................................................................................................................................4
Cancer Epidemiology in Nijmegen......................................................................................................6
Take home messages..........................................................................................................................6
LE Pathology (Femke Doubrava-Simmer)...............................................................................................6
Traditional clinical pathology..............................................................................................................7
Diagnosis........................................................................................................................................8
How do metastasis develop................................................................................................................9
Molecular pathology.........................................................................................................................10
LE Chemical Carcinogenesis..................................................................................................................11
Introduction/history.........................................................................................................................11
Biotransformation............................................................................................................................12
Transport..........................................................................................................................................13
Mechanisms.....................................................................................................................................15
Tests.................................................................................................................................................15
Regulation and prediction (REACH)..................................................................................................15
LE chemotherapy and receptor mediated therapy...............................................................................17
Introduction......................................................................................................................................17
Chemotherapy..................................................................................................................................17
Targeted therapy..............................................................................................................................18
Hormonal therapy............................................................................................................................19
Breast cancer: SERMs and aromatase inhibitors..........................................................................19
Prostate cancer.............................................................................................................................19
Clinical trials.....................................................................................................................................20
LE Genetic tumor susceptibility............................................................................................................21
Background.......................................................................................................................................21
, Cancer susceptibility in breast cancer..............................................................................................21
Cancer susceptibility in colon cancer................................................................................................22
LE Radiotherapy....................................................................................................................................23
Radiotherapy....................................................................................................................................23
Hypoxia.............................................................................................................................................24
4 combat hypoxia (research) examples............................................................................................24
LE Molecular Imaging of Cancer...........................................................................................................25
Medical imaging modalities..............................................................................................................25
Molecular imaging............................................................................................................................27
Radiotracers..................................................................................................................................27
Radionuclide imaging: PET & SPECT..............................................................................................27
New developments: molecular imaging of specific tumor markers..................................................29
PSMA: prostate cancer.................................................................................................................29
CAIXL: renal cell carcinoma...........................................................................................................29
PD-L1: personalized immune therapy...........................................................................................30
Development of new drug mechanisms.......................................................................................30
LE Organoids as a pre-clinical tool for cancer research........................................................................31
Introduction......................................................................................................................................31
Stem cells..........................................................................................................................................31
Organoids.........................................................................................................................................32
Applying CRISPR to organoids.......................................................................................................32
Co-culture.....................................................................................................................................32
LE Research of organoids in the lab......................................................................................................33
Deciphering colorectal cancer progression using colon tumor progression organoids....................33
Summary......................................................................................................................................33
Probing the function of the tumor suppressor Bap1 in liver tumor??..............................................33
Summary......................................................................................................................................34
Lecture 9: immunotherapy (uit samenvatting van Myrthe)..................................................................34
,LE introduction
Genetic alterations leads to unregulated cell growth invasion and spread to other parts of the body
Mutations, disturbed growth regulation, or invasive growth don’t always lead to cancer
Cancer is a multi-step process with different statuses with difference in biology, clinical management,
and treatment strategies.
LE cancer epidemiology (Alina Vrieling)
Descriptive cancer epidemiology
Life-time risk of cancer in females = 38% (1 in 3 females will develop cancer)
- Most common breast cancer
Life-time risk of cancer in males = 45% (almost 1 in 2 males will develop cancer)
- Most common prostate cancer
124,000 persons diagnosed with cancer every year in the Netherlands. This number is rising every
year, due to aging, population and lifestyle. A larger focus on preventable methods.
Knowledge about trends in incidence, survival and mortality is important for the development,
implementation, and evaluation of screenings and effective policies for cancer control.
Prevalence
Incidence
Incidence expressed in different ways:
- Number: absolute number of new cases in a certain period
- CR (crude rate): number of new cases per 100,000 persons per year
, - ESR (European standardized rate); the number of new cases per 100,000 persons per year,
standardized for the age composition of Europe
- WSR (world standardized rate): standardized for the age composition of the world
Mortality
Also expressed as number, CR, ESR or WSR
Relative survival
_
Worldwide differences in cancer e.g. liver cancer more in china and Africa, stomach caner in Russia
and asia, cervix cancer caused by HPV in africa.
Cancer incidence can vary per gender and per year:
- The incidence of lung cancer is increasing for females and decreasing in males
The mortality of cancer increases but the standardized mortality (standardized for age) decreases.
The relative survival increases (but differs per cancer type and stage
Etiology
How does cancer develop and what are the risk factors
Risk factors:
- Age (cancer rates increase with age until a certain age): time is needed for accumulation of
damage to your cells. Causes: mutations or damage to repair tools
- Chemical substances
- Radiation
- Viruses
Protective tools:
- DNA repair
- Apoptosis
- Senescence = mitosis stops
“grey” pressure:
25% increase in number of cancer diagnosis from 2007 to 2017. Also, survival improved, therefore
many more people living with cancer (49%).
Inhoudsopgave
LE introduction.......................................................................................................................................3
LE cancer epidemiology (Alina Vrieling)..................................................................................................3
Descriptive cancer epidemiology........................................................................................................3
Prevalence......................................................................................................................................3
Incidence........................................................................................................................................3
Mortality.........................................................................................................................................4
Relative survival..............................................................................................................................4
Etiology...............................................................................................................................................4
Cancer Epidemiology in Nijmegen......................................................................................................6
Take home messages..........................................................................................................................6
LE Pathology (Femke Doubrava-Simmer)...............................................................................................6
Traditional clinical pathology..............................................................................................................7
Diagnosis........................................................................................................................................8
How do metastasis develop................................................................................................................9
Molecular pathology.........................................................................................................................10
LE Chemical Carcinogenesis..................................................................................................................11
Introduction/history.........................................................................................................................11
Biotransformation............................................................................................................................12
Transport..........................................................................................................................................13
Mechanisms.....................................................................................................................................15
Tests.................................................................................................................................................15
Regulation and prediction (REACH)..................................................................................................15
LE chemotherapy and receptor mediated therapy...............................................................................17
Introduction......................................................................................................................................17
Chemotherapy..................................................................................................................................17
Targeted therapy..............................................................................................................................18
Hormonal therapy............................................................................................................................19
Breast cancer: SERMs and aromatase inhibitors..........................................................................19
Prostate cancer.............................................................................................................................19
Clinical trials.....................................................................................................................................20
LE Genetic tumor susceptibility............................................................................................................21
Background.......................................................................................................................................21
, Cancer susceptibility in breast cancer..............................................................................................21
Cancer susceptibility in colon cancer................................................................................................22
LE Radiotherapy....................................................................................................................................23
Radiotherapy....................................................................................................................................23
Hypoxia.............................................................................................................................................24
4 combat hypoxia (research) examples............................................................................................24
LE Molecular Imaging of Cancer...........................................................................................................25
Medical imaging modalities..............................................................................................................25
Molecular imaging............................................................................................................................27
Radiotracers..................................................................................................................................27
Radionuclide imaging: PET & SPECT..............................................................................................27
New developments: molecular imaging of specific tumor markers..................................................29
PSMA: prostate cancer.................................................................................................................29
CAIXL: renal cell carcinoma...........................................................................................................29
PD-L1: personalized immune therapy...........................................................................................30
Development of new drug mechanisms.......................................................................................30
LE Organoids as a pre-clinical tool for cancer research........................................................................31
Introduction......................................................................................................................................31
Stem cells..........................................................................................................................................31
Organoids.........................................................................................................................................32
Applying CRISPR to organoids.......................................................................................................32
Co-culture.....................................................................................................................................32
LE Research of organoids in the lab......................................................................................................33
Deciphering colorectal cancer progression using colon tumor progression organoids....................33
Summary......................................................................................................................................33
Probing the function of the tumor suppressor Bap1 in liver tumor??..............................................33
Summary......................................................................................................................................34
Lecture 9: immunotherapy (uit samenvatting van Myrthe)..................................................................34
,LE introduction
Genetic alterations leads to unregulated cell growth invasion and spread to other parts of the body
Mutations, disturbed growth regulation, or invasive growth don’t always lead to cancer
Cancer is a multi-step process with different statuses with difference in biology, clinical management,
and treatment strategies.
LE cancer epidemiology (Alina Vrieling)
Descriptive cancer epidemiology
Life-time risk of cancer in females = 38% (1 in 3 females will develop cancer)
- Most common breast cancer
Life-time risk of cancer in males = 45% (almost 1 in 2 males will develop cancer)
- Most common prostate cancer
124,000 persons diagnosed with cancer every year in the Netherlands. This number is rising every
year, due to aging, population and lifestyle. A larger focus on preventable methods.
Knowledge about trends in incidence, survival and mortality is important for the development,
implementation, and evaluation of screenings and effective policies for cancer control.
Prevalence
Incidence
Incidence expressed in different ways:
- Number: absolute number of new cases in a certain period
- CR (crude rate): number of new cases per 100,000 persons per year
, - ESR (European standardized rate); the number of new cases per 100,000 persons per year,
standardized for the age composition of Europe
- WSR (world standardized rate): standardized for the age composition of the world
Mortality
Also expressed as number, CR, ESR or WSR
Relative survival
_
Worldwide differences in cancer e.g. liver cancer more in china and Africa, stomach caner in Russia
and asia, cervix cancer caused by HPV in africa.
Cancer incidence can vary per gender and per year:
- The incidence of lung cancer is increasing for females and decreasing in males
The mortality of cancer increases but the standardized mortality (standardized for age) decreases.
The relative survival increases (but differs per cancer type and stage
Etiology
How does cancer develop and what are the risk factors
Risk factors:
- Age (cancer rates increase with age until a certain age): time is needed for accumulation of
damage to your cells. Causes: mutations or damage to repair tools
- Chemical substances
- Radiation
- Viruses
Protective tools:
- DNA repair
- Apoptosis
- Senescence = mitosis stops
“grey” pressure:
25% increase in number of cancer diagnosis from 2007 to 2017. Also, survival improved, therefore
many more people living with cancer (49%).
