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College aantekeningen Oncologie
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Aantekeningen HC OncologyHoorcollege 0 – Introductie
Boek is leidend maar wordt ook grootste deel in HC beschreven. Lectures are supporting the book.
Seminar niet te vinden in het boek, wel achtergrond via artikel etc maar dit is niet de leerstof.
Hoorcollege 1 – Chapter 1 introduction: The nature of cancer
Definitions:
- Incidence: number of new cases in a certain period (mostly 1 year, also per a certain amount
of people)
Full definition: The incidence of cancer is defined to be the number of new cases that is registered
within a certain period (mostly 1 year). To be able to follow the incidence in time, or to enable
comparison between regions, the incidence is mostly expressed as the number of new cases per
100.000 inhabitants/persons each year: the crude incidence rate.
- Prevalence: number of people who somewhere in time have been diagnosed with cancer
and still live at a certain date. For example the 5-year prevalence
Full definition: The prevalence of cancer comprises all persons who somewhere in time have been
diagnosed with cancer, and are still living at a certain date. So this is a diverse group, ranging from
persons who have been cured from cancer in the past to persons who just have been diagnosed with
cancer. As an example: the 5-year prevalence at January 1th 2010 comprises all still living cancer
patients who have been diagnosed with cancer during the previous 5 years
- Mortality: number of patients who died because of cancer
Full definition: The mortality of cancer comprises the number of patients who died as a result of
cancer within a certain period (mostly 1 year).
- Survival: percentage of patients who still live after a certain period after diagnosis.
Corrected by lifetime expectancy.
Full definition: Survival is the percentage of patients still living at a certain period after diagnosis. The
presented survival is a relative survival which approaches the “cancer-specific survival”. This means
that the survival observed is corrected for the expected death within the Dutch population
comparable with respect to gender, age and calendar year. Since survival can be strongly dependent
on age, also standardization for age-group is performed.
How many patients were diagnosed with cancer in the Netherlands in 2020: 115.000 (incidence)
→ 1/150
Life time → 1/3
5-year cancer prevalence (2020): > 380.000
Mortality (2019): > 46.000
Worldwide ~ 17,5 million
,HDI: mean income countries
Red= mortality Blue= incidence
Cancer mortality trends 2010 vs 2020
5 year survival rate 1970 vs 2010-2016
49% → 70%
What is the clinical definition of cancer?
• Cancer is a group of diseases.
• More than 100 cancer types can be distinguished (or even every tumour is different?).
• Uncontrolled cell growth.
• Invasive and forming metastases.
Benign tumours are not cancer!! Only when its invasive and metastases it’s a cancer
Malignant tumour is life threatening:
- Invasion of organs disturbs organ function
- Cancer cells compete with normal cells for nutrients and oxygen
- Growing tumour can cause obstruction
Different sides of origination:
- Carcinoma is from epithelia (85% of all cancers)
- Adenocarcinomas arise from glandular tissue (e.g. breast)
- Sarcomas arise from mesodermal tissue (e.g. bone, muscle)
- Lymphomas arise from (progenitors of) white blood cells
,Incidence carcinomas is much higher than other cancers, this is because of:
- Epithelial cells are highly proliferating cells, most abundant cells, highly metabolic active,
more exposed to carcinogens.
What is a carcinogen:
- A carcinogen is an agent causing cancer
- A carcinogen causes alterations in the DNA of a cell
- Cancer cells contain many alteration in het DNA
- The accumulation of mutations in the DNA causes stepwise development of cancer
(oncogenesis/carcinogenesis)
Cancer is clonal, tumors are heterogeneous
Is cancer inheritable?
• No. Almost all of the mutations develop in somatic cells and will not be passed to the next
generation of offspring.
• However, some inheritant germline mutations can increase the chance to develop cancer and can
be passed on to the next generation of offspring. These mutations are rarely involved in causing
cancer immediately (p53).
Development of cancer at older age:
- An accumulation of mutations in the DNA is needed for the development of cancer
- It is a matter of chance and time (exposure to carcinogens)
- The incidence of cancer is increasing due to longer life expectancy
Hallmarks of cancer:
Belangrijk! ^^
Tumor is more then only tumor cells. It also contains fibroblasts, immune cells, endothelial cells,
blood vessels etc.
The growth of a tumour is a disturbed balance between differentiation, cell death and proliferation.
For example apoptosis and differentiation are blocked and proliferation is expanded.
, Oncogenes
- Normal genes induced for expression by mutations
- The wild type genes are called proto-oncogenes
- Sometimes arising from viruses
Tumour suppressor genes
- Tumor suppressor genes protect against cancer
- Tumour suppressor genes have to lose function: loss of growth inhibition
Growth of a tumour
- Every healthy cell has two copies of a gene
- A mutation if an oncogene is dominant; 1 mutation is sufficient. Its protein product is
produced at higher quantities or increased activity
- A mutation in a tumour suppressor gene is recessive; most of the time both alleles need a
mutation
- An exception forms haploinsufficiency
The development of cancer is usually associated with a combination of:
Mutation of one copy of proto-oncogene and loss of both copies of tumour suppressor gene.
Identification of oncogenes
- Isolation of the gene from tumour cells
- Transfection of DNA into immortalized mouse fibroblasts
- Evaluation whether transfected cells obtain altered growth characteristics (transformation
assay)
Factors playing a role in development of cancer:
- Environment (soot, sunlight, asbestos).
- Diet (fruit and vegetables, fish) and exercise.
- Alcohol (head and neck, breast).
- Smoking (>80 carcinogenes; 40% of all cancer deaths).
- Reproduction, contraception, hormone replacement therapy.
- Viruses (sexual transmittable).
- Own metabolism (by-products of metabolism and errors in DNA replication).
What are the limitations of conventional chemotherapy?
• Adverse events/toxicity on normal tissues.
• The therapeutic index of most of the chemotherapeutics is relatively small.
The therapeutic index is the difference between maximum tolerated dose (MTD) and the minimum
dose needed to exert anti-cancer activity
Clinical trials with novel anticancer agents
• New experimental anti-cancer agents have first to be tested in patients without any further
treatment options. Three phases of evaluation have to be passed:
• Phase I: Assessment of safety in a limited number of patients. [Also assessment of
pharmacokinetics (target engagement) and metabolism.]
• Phase II: Assessment of efficacy at a safe dose.
• Phase III: Extensive trials (hundreds to thousands of patients). Assessment of added value.
Comparison with current standard treatment.
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