(PM3B) Introduction to Cancer Flashcards
What features do all cancers share?
Uncontrolled cell growth + invasion
How are cancers classified?
Usually based on:
(1) Where the cancer arises in the body
(2) The type of cell affected
What is cancer of epithelial tissue?
Carcinoma
What is cancer of connective tissue?
Sarcoma
What is cancer of bone marrow?
(1) Myeloma – plasma cells
(2) Leukaemia – RBCs + WBCs
What is cancer of the lymph nodes or glands?
Lymphoma
What does the suffix ‘oma’ refer to?
Benign tumours
What does the prefix adeno- mean?
Of a gland
What does the prefix chondro- mean?
Of cartilage
What does the prefix erythro- mean?
Of RBCs
What does the prefix hemangio- mean?
Of the blood vessels
What does the prefix hepato- mean?
Of the liver
What does the prefix lipo- mean?
Of the fat
What does the prefix lympho- mean?
Of the lymph nodes
What does the prefix melano- mean?
Of the pigment cells (melanocytes)
What does the prefix myelo- mean?
Of the bone marrow
What does the prefix myo- mean?
Of the muscle
What does the prefix osteo- mean?
Of the bone
Name some of the cancers with the best prognosis.
(1) Nonmelanoma of the skin
(2) Prostate
(3) Testis
(4) Melanoma
What does neoplasm mean?
A new disorganised growth
Excessive + uncontrolled growth
Synonymous with tumour
What is a tumour?
An abnormal mass of cells
What are benign tumours?
Enlarge but do not spread beyond their initial site
Do not invade surrounding tissues
What are malignant tumours?
Spread beyond their initial site
Can be very dangerous
What is metastasis?
Invasion of tumour to surrounding tissue
Spread beyond initial site
What is carcinogenesis?
Process of forming a cancer
via carcinogens
What are the stages of tumorigenesis?
(1) Normal tissue
(2) Initiated tumour growth
(3) Mild tumour growth
(4) Moderate tumour growth
(5) Severe tumour growth
(6) Carcinoma in situ
(7) Cancer
What are the phases of the cell cycle?
(1) M Phase – mitosis + cytokinesis
(2) GAP 0 –resting cells
(3) GAP 1 – RNA + protein synthesis required for S phase
(4) S Phase – DNA synthesis
(5) GAP 2 – RNA + protein synthesis required for M phase
What stages are included in the M phase?
(1) Prophase
(2) Metaphase
(3) Anaphase
(4) Telophase
What are the stages of mitosis?
(1) Prophase
(2) Metaphase
(3) Anaphase
(4) Telophase
What is prophase?
Stage of mitosis (M Phase)
(1) Chromosomes condense
(2) Centrosomes assemble
(3) Nuclear membrane begins to break down
What is metaphase?
Stage of mitosis (M Phase)
(1) Chromosomes align and attach to spindle
What is anaphase?
Stage of mitosis (M Phase)
(1) Chromotids pull apart and migrate to poles
What is telophase?
Stage of mitosis (M Phase)
(1) Chromotids de-condense
(2) New nuclear membrane forms
What is cytokinesis?
Stage of mitosis (M Phase)
(1) Nuclear membrane completely surrounds decondensed chromosomes
(2) Contractile ring pinches off
(3) Divides cytoplasm of mother and daughter cells
When is the cell cycle regulated?
Midpoint of GAP 1 (G1) phase
By extracellular signals
How is the cell cycle regulated?
Extracellular signals
In the GAP 1 (G1) phase
What are the cell cycle checkpoints?
(1) M Phase – anaphase – blocked if chromatids are not correctly assembled on mitotic spindle
(2) Late GAP1 (G1) Phase – DNA damage checkpoint – entrance to S phase is blocked if genome is damaged
(3) Mid S Phase: DNA damage checkpoint – DNA replication is halted if genome is damaged
(4) Late GAP 2 (G2) Phase – entrance into M Phase is blocked if replication is not complete
What protein complex is required to progress to S phase from GAP 1 (G1)?
D-CDK4/6
What protein complex is required to progress to GAP 2 (G2) phase from S Phase?
A-CDC2
What protein complex is required to progress to M Phase from GAP 2 (G2) Phase?
B-CDC2
Which stage of the cell cycle can be influenced by extracellular signals?
GAP 1 – G1 phase
What role does cyclin play in the cell cycle?
Regulation relies on cyclin and cyclin-dependent kinases
Which factors control regulatory cyclin expression?
(1) E2F transcription factors
(2) pRB proteins
Which factors control regulatory cyclin CDK complexes?
Phosophorylation + dephosphorylation by other cyclin-dependent kinases
How can cyclin-dependent complexes be inhibited?
Directly inhibited by cyclin-dependent kinase inhibitors
e.g. protein 27 (p27)
Who established the hallmarks of cancer?
Robert Weinberg
What are the hallmarks of cancer?
(1) Sustaining proliferative signalling
(2) Evading growth suppressors
(3) Activating invasion + metastasis
(4) Enabling replicative immortality
(5) Inducing angiogenesis (development of new blood vessels)
(6) Resisting cell death (apoptosis)
How do cancer cells gain growth factor independence?
Gain an oncogene, lose necessity for external growth factors
Can be in a number of ways:
(1) Secretion of growth factor normally secreted by surrounding tissue
(2) Mutation in growth factor receptor so it is constantly activated
(3) Mutation of components of signalling pathways
(4) Mutation of transcription factors activated by growth factors
What is an oncogene?
Genes which, when mutated or overexpressed, can cause cancer
Mutations in proto-oncogenes lead to a gain of function
Often involved in the regulation of cell proliferation
How can oncogenes lead to a potential gain in function?
Mutations in proto-oncogenes lead to a gain of function
Give an example of a proto-oncogene.
Ras
What role does Ras play in cell proliferation?
(1) In presence of growth factors is activated
(2) Triggers other signalling events
(3) Signalling events lead to cell proliferation
Give some examples of oncogenes, other than Ras.
(1) Bcr-Abl
(2) Myc
(3) Src
(4) PI3 kinase
What is HER2?
Human epidermal growth factor receptor 2
What can be said about HER2 positive cancers?
Typically more aggressive
Associated with early progression + recurrence + poor prognosis
Name an inhibitor of HER2.
Trastuzumab (Herceptin)
What is trastuzumab?
Herceptin
Inhibitor of HER2
How may cell insensitivity to growth inhibitors arise?
Result from alterations in cell cycle regulation
- Loss of tumour suppression genes
- Upregulation of positive cell cycle regulators, e.g. cyclins
How many ‘hits’ are typically required to inactivate a tumour suppressor gene?
2 hits
Name some examples of tumour suppressor genes.
(1) pRB
(2) p53
(3) BRCA
How do tumour suppressor genes function?
Detection of DNA damage + mutations
Triggers apoptosis or DNA repair
What is the most common human mutated gene in cancer?
Protein53
p53
What signalling roles does p53 have in the body?
(1) Cell cycle arrest
(2) DNA repair
(3) Block of angiogenesis
(4) Apoptosis
What shortens with every cell division?
Telomere
Why can cells only proliferate 40-60 times?
Telomere length shortens
In which cell types do telomeres not shorten, following proliferation?
(1) Stem cells
(2) Cancers
Why does the telomere of a cancerous cell not shorten?
Rebuild telomeres
Using telomerase
Which mechanism do radiotherapy and chemotherapy exploit to kill cancer cells?
Apoptosis
How are cancer cells able to avoid apoptosis?
(1) Gain of function (over-expression) of pro-survival factors (i.e. IGF)
(2) Loss of function of pro-apoptotic factors (i.e. p53)
Give an example of a pro-apoptotic factor.
p53
Protein53
How does IGF1 promote cancer development?
(1) Inhibits apoptosis
(2) Stimulates cell proliferation
Which types of cancer may be more resistant to therapy?
Cancers which are able to avoid apoptosis
What keeps tumours small initially?
Lack of blood supply
How do cancer cells promote blood vessel growth (angiogenesis)?
Secretion of angiogenic factors
e.g. Vascular Endothelial Growth Factor (VEGF)
(OR)
Fibroblast growth Factor (FGF)
How do cancer cells reach the blood supply?
‘Crawl’
Through the extracellular matrix (ECM)
What are some potentially emerging hallmarks of cancer?
(1) Deregulating cellular energetic
(2) Avoiding immune destruction
(3) Genome stability + mutation
(4) Tumour-promoting inflammation
What are some ways that cancer is able to kill?
(1) Muscle wasting
(2) Interferes with metabolic processes
(3) Interferes with normal organ function
What are some ways that cancer interferes with normal organ function?
(1) Blockage/ obstruction
(2) Deprivation of nutrients
(3) Pressure
What are some ways that cancer interferes with metabolic processes?
(1) Malnutrition
(2) Calcium changes
(3) Liver enzyme function
(4) Production of blood cells
(5) Hormone production
What is the Knudson hypothesis?
That cancer is the result of an accumulation of mutations to DNA of a cell
Which hallmarks does a cell need to meet to progress to cancer?
Most/ all of the hallmarks
Which key types of gene, that when mutated, can lead to cancer?
(1) Proto-oncogenes
(2) Tumour suppressor genes
What are the nucleotide base pairs?
Cytosine–Guanine (3 bonds)
Thymine–Adenine (2 bonds)
What types of mutation can occur in a cell?
(1) Point mutations or small insertions/deletions in gene coding regions
(2) Alterations in transcription/splicing
(3) Amplifications/deletions of chromosomal regions
(4) Chromosomal translocations
(5) Gains and losses of whole chromosomes
(6) Changes in DNA modification, e.g. DNA methylation
What are some potential causes of mutations?
(1) UV/ radiation
(2) Free radicals from metabolic processes
(3) Viruses
(4) Chemicals – smoking/ asbestos etc
(5) Copying/ repair errors (inheritable)
What are the stages in cancer development?
(1) Initiation –first mutations promoting proliferation (carcinogenesis)
(2) Promotion – additional mutations promote further proliferation (carcinogenesis)
(3) Tumour progression – growth + invasion of tumour
What is carcinogenesis?
First 2 stages of cancer progression
Initiation + promotion
Why is identification of tumour progression important?
Determination of treatment + prognosis
What are the stages that cancer tumours are put into?
(1) Stages 1-4
(2) TNM scheme
What is the TNM scheme?
(1) T = Tumour –how far the tumour has grown locally; score 1-4
(2) N = Nodes – is there any invasion to lymph nodes; score 0-2
(3) Metastasis – has the tumour spread to distant sites; score 0 or 1
Which organs have the lowest survival rates in cancer development?
(1) Pancreas
(2) Lung
(3) Oesophagus
Why are cancer survival rates improving?
Earlier diagnosis due to:
- Screening
- Scanning
- Biomarkers
Better treatment due to:
- Surgery
- Radiotherapy
- Chemotherapy
Name some cancers that can be self-checked for early diagnosis.
(1) Breast cancer
(2) Skin cancer
(3) Testicular cancer
What are some current NHS screening programmes?
(1) Bowel cancer (60-75yrs old)
(2) Cervical cancer (25-65yrs old women)
(3) Breast cancer (50-70yrs old women)
What are some risk factors for cancer?
(1) Smoking
(2) Alcohol
(3) Obesity
(4) Inactivity
(5) Poor diet
(6) Infections – cause 18% of cancers globally
