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Lecture notes Cancer Biology & Treatment - AUC

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Lecture notes and chapter summaries of all course material covered in Cancer Biology & Treatment at Amsterdam University College.

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  • 4 augustus 2024
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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)

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