Cancer Biology & Treatment (AUC)
LECTURE 1
Introduction 06-09
- Incidence is number of new cases in a certain period per region
o Also recorded as number of cases per 100000 inhabitants
- Prevalence is all persons who have been diagnosed with cancer and are still alive at a certain date
- Mortality is number of people who died as a result of cancer in a certain period
- Survival is percentage of patients who are still alive at a certain period after diagnosis
o Corrected for expected death
What is cancer
- Large group of diseases (more than 100 types)
- Characterised by uncontrollable cell growth, invasiveness, and growing metastasis
- Only malignant tumours are cancer
Why is a malignant tumour so dangerous
- Disturb organ function
- Compete with normal cells for nutrients and oxygen
- Can cause obstructions (eg. No blood flow to organ)
Carcinomas: arise from epithelial cells
Adenocarcinomas: from glandular tissues
Sarcomas: from mesodermal tissue (bone and muscle)
Lymphomas: from white blood cells
Why are carcinomas so prevalent
- Exposed more to carcinogens
o Compound, radiation
o Induces mutations in DNA
o Accumulation of DNA mutations can cause development of cancer
Factors playing a role in cancer development
- Environment (sunlight, asbestos)
- Diet & exercise (fish, fruit can help)
- Alcohol
- Smoking -> also causes other cancers
- Hormones
- Viruses
- Own metabolism
Early on you get mutations that deregulate growth
, - Then more cells grow and one may accumulate more mutations
- This goes on to form a heterogeneous and clonal tumour
o Heterogeneous because different mutations -> makes treatment difficult
o Clonal because all stem from one cell
Inheritability
- You cannot really inherit cancer but you can inherit mutations from germline cells that can put you at
a higher risk for cancer
Why does risk for cancer increase in age
- Allows time for accumulation of mutations in DNA
- Matter of chance and time (exposure from carcinogens
- Third one on slide
Hallmarks of cancer (characteristics that all cancers have
Ten hallmarks in book -> very important (can get question on this in exam)
A tumour is more than just a bulk of cells
- Tumour microenvironment includes blood vessels, normal cells, immune cells
Oncogenesis reverts differentiated cells back to a more stem cell type
- Goes to more primitive cell type that can only proliferate
Tumour suppressor genes stimulate differentiation
Oncogenes
- Often normal genes (sometimes come from viruses)
- The normal genes are called proto-oncogenes
What do you need for a tumour to develop
- Need oncogene
- Need tumour suppressor gene to lose its function
Can we see difference between normal and cancer cells
- Cancer cells have a different morphology
- Cancer cells can grow at low serum (not much growth factor) in culture media
- Cancer cells have decreased contact inhibition
- Cancer cells do not need substrate for attachment
How can we identify oncogenes
- Isolate genes from tumour cells
- Transfect this into normal cells
- See whether the growth of these cells is different
Homework: find out if there is an easier way of identifying these oncogenes
,Treatment of cancer
- Surgery
- Radiotherapy
- Chemotherapy
- Cytostatic treatment
- Cytotoxic treatment
Treatments have toxicity to normal tissue cells
- Need to stay within the therapeutic window -> all possible doses that are therapeutic and cause no
horrible toxicity
- Therapeutic index is the ratio of dosage at 50% damage to normal cells to the dosage at 50% of
damage to cancer cells
Every hallmark is a potential target for selective therapy
Only small proportion of patients (25%) benefits from cancer treatment
- Important to know which patients benefit from certain treatments
- Figure out before which treatments cannot help certain people -> no unneeded costs and side effects
- Diagnostics!! Responsiveness can be predicted by genetics
, CHAPTER 1
General Introduction
What is cancer?
The six hallmarks of cancer
- Growth signal autonomy
o Cancer cells do not need growth factors to divide like normal cells
- Evasion of growth inhibitory signals
o Cancer cells do not respond to growth inhibitory signals
- Unlimited replicative potential
o Normal cells have a limit to replicating potential due to the shortening of telomeres
o Cancer cells retain the length of their telomeres and therefore can replicate infinitely
- Invasion and metastasis
o Migration of cancer cells is a huge cause of death, healthy cells usually do not migrate
- Angiogenesis
o Cancer cells induce angiogenesis for a better supply of nutrients and oxygen
- Evasion of cell death
o Cancer cells avoid apoptotic signals so they are not killed
Two enabling characteristics of cancer
- Tumour promoting inflammation
o Inflammation can help tumours by providing growth factors and enzymes that stimulate
angiogenesis and invasion, they can also release ROS to help create mutations in cells
- Genome instability and mutation
o Mutations in DNA and inability to fix these usually leads to the 6 hallmarks of cancer
Especially when the mutations are related to growth factors
Two emerging hallmarks of cancer
- Avoiding immune destruction
o There is evidence that the immune system can recognize cancer cells
o Successful cancer cells do not stimulate such immune response or are able to interfere with it
to avoid destruction
- Reprogramming energy metabolism
o Adjusting energy metabolism is needed to keep up with the demands of rapidly dividing
cancer cells
Benign and malignant tumours
- Benign tumours don’t metastasize and are therefore no evidence of cancer
o They can be life threatening due to their location (in the brain for instance)
- Malignant tumours show features of invasion and metastasize (movement through the body)
Cancer cells in culture
- They don’t grow as a sheet, rather as an uncontrollable pile
- They can grow in low serum since they do need much growth factor
- They have a different morphology (more round rather than flat)
LECTURE 1
Introduction 06-09
- Incidence is number of new cases in a certain period per region
o Also recorded as number of cases per 100000 inhabitants
- Prevalence is all persons who have been diagnosed with cancer and are still alive at a certain date
- Mortality is number of people who died as a result of cancer in a certain period
- Survival is percentage of patients who are still alive at a certain period after diagnosis
o Corrected for expected death
What is cancer
- Large group of diseases (more than 100 types)
- Characterised by uncontrollable cell growth, invasiveness, and growing metastasis
- Only malignant tumours are cancer
Why is a malignant tumour so dangerous
- Disturb organ function
- Compete with normal cells for nutrients and oxygen
- Can cause obstructions (eg. No blood flow to organ)
Carcinomas: arise from epithelial cells
Adenocarcinomas: from glandular tissues
Sarcomas: from mesodermal tissue (bone and muscle)
Lymphomas: from white blood cells
Why are carcinomas so prevalent
- Exposed more to carcinogens
o Compound, radiation
o Induces mutations in DNA
o Accumulation of DNA mutations can cause development of cancer
Factors playing a role in cancer development
- Environment (sunlight, asbestos)
- Diet & exercise (fish, fruit can help)
- Alcohol
- Smoking -> also causes other cancers
- Hormones
- Viruses
- Own metabolism
Early on you get mutations that deregulate growth
, - Then more cells grow and one may accumulate more mutations
- This goes on to form a heterogeneous and clonal tumour
o Heterogeneous because different mutations -> makes treatment difficult
o Clonal because all stem from one cell
Inheritability
- You cannot really inherit cancer but you can inherit mutations from germline cells that can put you at
a higher risk for cancer
Why does risk for cancer increase in age
- Allows time for accumulation of mutations in DNA
- Matter of chance and time (exposure from carcinogens
- Third one on slide
Hallmarks of cancer (characteristics that all cancers have
Ten hallmarks in book -> very important (can get question on this in exam)
A tumour is more than just a bulk of cells
- Tumour microenvironment includes blood vessels, normal cells, immune cells
Oncogenesis reverts differentiated cells back to a more stem cell type
- Goes to more primitive cell type that can only proliferate
Tumour suppressor genes stimulate differentiation
Oncogenes
- Often normal genes (sometimes come from viruses)
- The normal genes are called proto-oncogenes
What do you need for a tumour to develop
- Need oncogene
- Need tumour suppressor gene to lose its function
Can we see difference between normal and cancer cells
- Cancer cells have a different morphology
- Cancer cells can grow at low serum (not much growth factor) in culture media
- Cancer cells have decreased contact inhibition
- Cancer cells do not need substrate for attachment
How can we identify oncogenes
- Isolate genes from tumour cells
- Transfect this into normal cells
- See whether the growth of these cells is different
Homework: find out if there is an easier way of identifying these oncogenes
,Treatment of cancer
- Surgery
- Radiotherapy
- Chemotherapy
- Cytostatic treatment
- Cytotoxic treatment
Treatments have toxicity to normal tissue cells
- Need to stay within the therapeutic window -> all possible doses that are therapeutic and cause no
horrible toxicity
- Therapeutic index is the ratio of dosage at 50% damage to normal cells to the dosage at 50% of
damage to cancer cells
Every hallmark is a potential target for selective therapy
Only small proportion of patients (25%) benefits from cancer treatment
- Important to know which patients benefit from certain treatments
- Figure out before which treatments cannot help certain people -> no unneeded costs and side effects
- Diagnostics!! Responsiveness can be predicted by genetics
, CHAPTER 1
General Introduction
What is cancer?
The six hallmarks of cancer
- Growth signal autonomy
o Cancer cells do not need growth factors to divide like normal cells
- Evasion of growth inhibitory signals
o Cancer cells do not respond to growth inhibitory signals
- Unlimited replicative potential
o Normal cells have a limit to replicating potential due to the shortening of telomeres
o Cancer cells retain the length of their telomeres and therefore can replicate infinitely
- Invasion and metastasis
o Migration of cancer cells is a huge cause of death, healthy cells usually do not migrate
- Angiogenesis
o Cancer cells induce angiogenesis for a better supply of nutrients and oxygen
- Evasion of cell death
o Cancer cells avoid apoptotic signals so they are not killed
Two enabling characteristics of cancer
- Tumour promoting inflammation
o Inflammation can help tumours by providing growth factors and enzymes that stimulate
angiogenesis and invasion, they can also release ROS to help create mutations in cells
- Genome instability and mutation
o Mutations in DNA and inability to fix these usually leads to the 6 hallmarks of cancer
Especially when the mutations are related to growth factors
Two emerging hallmarks of cancer
- Avoiding immune destruction
o There is evidence that the immune system can recognize cancer cells
o Successful cancer cells do not stimulate such immune response or are able to interfere with it
to avoid destruction
- Reprogramming energy metabolism
o Adjusting energy metabolism is needed to keep up with the demands of rapidly dividing
cancer cells
Benign and malignant tumours
- Benign tumours don’t metastasize and are therefore no evidence of cancer
o They can be life threatening due to their location (in the brain for instance)
- Malignant tumours show features of invasion and metastasize (movement through the body)
Cancer cells in culture
- They don’t grow as a sheet, rather as an uncontrollable pile
- They can grow in low serum since they do need much growth factor
- They have a different morphology (more round rather than flat)
