Summary
Samenvatting Oncology
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An abstract summary about the first six chapters.
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Chapter 1Cancer is a disease that is characterized by
- Unregulated cell growth
- Invasion and spread of cells
Tumor
- A tumor is a mass of cells
- Not every tumor is invasive and metastasizing
- Benign tumors are not cancer
Malignant tumor can be life threatening because
- Obstructive prosperities (organs, arteries)
- Can compete with normal cells for nutrients and oxygen
- Invasion of organs can disturb an organ’s function
85% of cancer occurs in epithelial cells
Classification
Epithelial carcinoma
White blood cell lymphoma
Mesoderm sarcoma
Glandular tissue adenocarcinoma
Hallmarks of cancer
- Autonomous growth signals
- Evasion of growth inhibitory signals
- Evasion of apoptic cell death
- Unlimited proliferative potential
- Angiogenesis
- Invasion and metastasis
New hallmark
- Genome instability
- Tumor promoting inflammation
- Reprogramming energy metabolism
- Avoiding immune destruction
Carcinogen agent that causes cancer
Mutagen agent that causes a mutation in the DNA sequence
Alterations in DNA
- Point mutation
- Chromosomal abberations
o Deletions
o Translocations
Oncogenesis
- Clonal and heterogenous
o Origin of cancer
, One cell contains a mutation and will be cloned
Subclones get other mutations and will cause for the heterogeneity
-
Accumulation of mutations only occur when a cell’s defense mechanism has been evaded
Mutation that alters the function of normal genes can lead to unregulated growth
The genes involved in
- Growth
- Apoptosis
- Differentiation
There are two types of mutated genes that play an important role in carcinogenesis
- Oncogenes
o Protein product will be produced in higher quantity or increased activity
o One mutation is dominant
- Tumor suppressor genes
o Proteins play a role in inhibiting growth and tumor formation
Loss of growth inhibition due to loss of function of these genes
Mainly recessive because one intact allele can still inhibit growth
o Predisposition for cancer occurs if someone inherits one mutated allele
If a somatic mutation occurs during life time cancer will develop at an
earlier age than sporadic cancer
Influential factors in carcinogenesis
- Environment
o Chronic exposure to siit
o Exposure to UV
- Reproductive life
o Children reduce chance of breast cancer development
o Age of reproduction
o Age of menarche
o Use of hormone replacement therapy
- Diet and exercise
- Alcohol
o Increased risk in mouth, esophagus, liver and breast cancer
o Increased combined risk with smoking
- Smoking
o Lung cancer
o 40% of all cancer deaths
Cancer therapies
- Earliest therapy was surgical removement of as much as possible cancerous tissue
- Additional chemo and radiotherapy have been used to inhibit or eradicate
metastasized cells
, Goals of therapy
- cytostatic
o Prevent proliferation
- Cytotoxic
o Kill cancer cell
- Effective result with the minimum side effects.
Therapeutic index is the value of the difference between the minimum effective doss and
the maximum tolerated dose. The larger the therapeutic index, the safer the drug
o The index is usually relatively small with chemotherapeutics
o
Therapeutic window
- Difference between maximum tolerated dose and the minimum dose needed to
exert anti-cancer window
-
Chemotherapy uses chemicals that target DNA, RNA and protein to disrupt the cell cycle in
rapid dividing cells. The specificity is broad. The goal is to cause so much damage that
apoptosis is triggered in cancer cells.
, Side effects occur in other fast going cells
- Hair follicles hair loss
- Stomach epithelia ulcer
- Hematopoietic cells anemia
Clinical trials
Phase I
- Dose responses in healthy individuals
Phase II
- Efficacy in larger population
Phase III
- Efficacy tested against conventional treatment
Molecular targets in cancer therapies
- Kinases
o Phosphorylate a hydroxyl group on specific amino acids in proteins.
Conformational change and important for (in)activation of a protein
o Functions
Signal transduction
Cell cycle progression
Transcription
- Phosphatases
o Removes phosphate group
- Ras protein
o Intracellular transducer protein that becomes active after a growth factor
binds to a receptor.
o A G-protein that resides at the intracellular part of a plasma membrane. After
activation GDP is transformed into GTP
- Tumor protein p53
o Guard of the genome
Tumor suppressor gene
o Responds to cell stresses
Cell cycle arrest
DNA repair
Apoptosis
o Acts as a transcription factor
- The retinoblastoma gene
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