TOPIC F: Cancer Flashcards
What are the physical characteristics of a cancer cell compared to a normal cell
Enlarged nucleus Changes to cytoskeleton Loss of specialised features Little cytoplasm Evidence of mitosis
No growth constraints (not limited by neighbouring cells or environment)
No physical attachment
What is a carcinoma
A cancer arising from epithelial cells of the skin and lining of organs
85% of all cancers
breast, lung, colon cancers
What is a sarcoma
Cancers arising from bone, muscle and blood vessels
What is a Lymphoma
Cancer arising from lymphoid cells and leukemias from white cells of the bone marrow
Do cancer cells require growth factors
No, can have greatly reduced requirement for growth factors
What is the relationship between cancer cells and telomeres
Cancer cells have chromosomal aberrations
- change in no. of chromosomes
- change in chromosome structure
Telomere shortening regulates how many round of cell division can occur. Cancer cells can ignore telomere shortening and keep dividing
What are the basic transitions of cancer progression
A single mutant cell
to a tumour
to metastasis (cancer spreads throughout body)
At least 4-6 mutations to reach the tumour state. process can decades for single mutant cell to proliferate into palpable tumour
What are the 2 types of tumours
Benign: look like original tissues. Localised (do not spread). Don’t cause problems unless in confined space (like brain)
Malignant: Do not look like original tissue. Physical changes, spread
Explain metastasis
When cancers invade other issues and spread throughout body.
Depends on type of cancer
Takes a lot of energy to proliferate and spread so angiogenesis occurs
Explain angiogenesis
The mechanism where tumours direct capillaries to travel into the tumour so it can have nutrients and oxygen for growth.
Angiogenesis can be targeted to stop cancer from growing
What are some of the implications of cancer genetic alteration
Increased cell growth
Resistance to apoptosis
Altered tissue invasiveness
Angiogenic proliferation
Ability to escape immune surveillance
What are 2 main causes of cancer
DNA damage
Viruses
Explain the types of DNA damage that can lead to cancer
Inherited (germ lime errors): every cell in body carries one copy of DNA with defect. 10% of cancers
Acquired (somatic errors): may lead to cancer in that tissue. only cancer cells carry mutation
How can acquired DNA damage leading to cancer be caused
Environmental exposure to:
radiation
viruses
bacteria
chemical carcinogenesis
age and diet
UV light
Cancer cells accumulate more and more errors over time. Why does this occur?
Ususally DNA repair enzymes can correct but
- substantial mutations
- loss of DNA repair enzymes
- less time for repair mechanism (rapid cell cycle to divide)
can lead to further DNA damage
Explain how viruses can lead to cancer
Infectious agents like viruses are causal agents in some cancers.
15% of cancers like nasopharynx, cervical, liver and lymphomas
Explain what an oncogene, tumour suppressor gene, mismatch repair gene, and proto-oncogene are.
Oncogene: promotes cancer
Tumour suppressor gene: act to prevent cancer
Mismatch repair gene: repair mutated DNA
Proto-oncogene: Normal genes that promote cell growth and division that could become an oncogene
What mutations can occur on a proto-oncogene
Deletion or point mutation = hyperactivity
Gene amplification = normal protein overproduced
Chromosome rearrangement = changes in regulation
Oncogenes are dominant meaning…
that one gain-of-function mutation can predispose a cell to cancer as it overrides the rest of cellular function
What cell functions are tumour suppressor genes involved in
Control cell cycle check points
Induce transcription of regulatory inhibitory genes
Overall, negatively control cell growth
What mutation can occur for a tumour suppressor gene
Loss of function mutation
Can be inherited or acquired
Both copies of gene must be lost for cancer to develop (two hit hypothesis)
Explain the two hit hypothesis
Loss of one copy of a tumour suppressor gene causes a slight cell progression advantage
Loss of both copies causes complete inactivation, significant growth advantage and predisposition to cancer
What is retinoblastoma
Rare childhood tumour of the retina (neural precursor cells of retina)
Caused by non-function retinoblastoma (Rb) tumour suppressor gene
2 forms: hereditary and sporadic
Both copies of gene must be lost
Explain the 2 types of retinoblastoma
Hereditary: young age, tumours in both eyes, mutant Rb allele on chromosome 13 in every cell of body
Non-hereditary/sporadic: 1 tumour in 1 eye, later age, mutant only in tumour cells
What are the usual cell functions of p53
master regulator of cell death
cell cycle arrest
senescence
cell differentiation
apoptosis
DNA repair
How does p53 cause cell death
Inducing selective gene expression to inhibit cell growth or induce apoptosis
stabilising p53 protein leads to increase in p53 levels
What are the results of p53 mutation
Chromosomes become fragmented, incorrectly rejoined
Successive cell divisions produce largely mutated genome
Explain MMR genes roles in cancer and mutation
8 MMR genes including MSH, MLH, PMS
Often lost or defective in cancers
2 hit hypothesis
What does hereditary cancer motivate
routine screening for cancers
genetic counselling
What are some of the features of inherited cancer
Several close relatives with common or related cancers
2 family members have the same rare cancer
Early age onset
Bilateral cancers in paired organs
Tumours in 2 different organs
What is penetrance
The percentage of individuals with specific genetic defect who will get the disease
Varies depending on gene
What are some features of inheritance of BRCA 1 and 2 breast cancers
Mutliple early onset cases in family
Breast and ovarian cancer history
Breast and ovarian cancer in same woman
Bilateral breast cancer
Ashkenazi jewish heritage
Male breast cancer
Explain tyrosine kinase receptor as an oncogene
Mutation or over-expression can cause cellular transformation (cancer) as they are involved in activating multiple oncogenes
Outline chronic myeloid leukemia (CML)
Leukemic cells have 9:22 translocation causing abnormal tyrosine kinase receptors
Arises from single abnormal hematopoietic stem cell
Proliferation of immature white blood cells
CML cells proliferate unchecked leading to
- bone marrow replacement
- increased liver size
- white blood cell increase
What is the Philadelphia chromosome
Shortened chromosome 22
End of chromosome 9 (containing abnormal tyrosine kinase) dused with B cell receptor (BCR) on chromosome 22
Fusion of bcr-abl produces a fusion protein which increases tyrosine kinase compared to normal and causes leukemia
How can CML be diagnosed
demonstration of chromosomal translocation by standard cytogenetics, FISH or PCR
What are the 3 main types of cancer treatment
Chemotherapy: kills rapdily dividing cells but also normal cells
Surgery: Cut cancer out, not always possible
Targeted therapies: find molecular cause and design therapies
For cancers with TKR signalling like CML what are some treatment strategies
ATP - competitive inhibitors: stop TKR binding to ATP, blocking activity
Other anti-TK drugs: Antibodies against receptor or ligands, blocking activation
Antibodies against RTK or lignads: Block ligand binding, receptor internalisation
Anti-angiogenics: TK inhibitors as a target for anti-angiogenesis
