STA: Cancer Flashcards
(42 cards)
What is the incidence of cancer?
1 in 2
Approx 375,000 new cases of cancer every year in the UK
Define cancer
- Abnormal cells divide in uncontrolled way
- Abnormal cells have potential to
- Form tumour, Invade neighbouring tissues, Spread to distant tissues (metastasise)
Outline the normal cell cycle and the signals cells must receive to undergo cell division
- Cells must receive positive signals to divide (e.g growth factors, Hormones)
- There are also signals telling a cell not to divide:
- Contact inhibition - surrounded by other cells, no need for new cells at the moment
- DNA damage response - Something is wrong with your DNA, cells shouldn’t divide until the DNA is repaired
- Cell division is controlled by the cell cycle - This is regulated by a range of signalling pathways, coded for by many genes, but mutations in these genes can lead to cancer
- Gap/Growth 1 (G1) - Longest phase, cell grows while organelles function as usual, terminates at G1 checkpoint
- Cells with damaged DNA → G0 phase/apoptosis
- Synthesis (S) - DNA replicated (identical chromatids created)
- Gap/Growth 2 (G2) - Organelles duplicated, Terminates at G2 checkpoint
- G1 + S + G2 = Interphase
- Mitosis (M) phase - Cell divides into 2 daughter cells
- There are also signals telling a cell not to divide:
What internal and external factors cause DNA to be constantly mutated?
- Interally:
- Reactive oxygen species (oxidative damage)
- Ineffective DNA repair mechanisms
- Externally:
- UV light
- Ionising radiatioon
- Cigarette smoke
- Chemical consumption
What do proto-oncogenes do?
Involved in positive control of cell growth and division
These have the potential to become oncogenes
What are oncogenes?
Mutated form of proto-oncogens
What are the main classes of proto-oncogenes?
Class I: Growth Factors
Class II: Receptors for Growth Factors and Hormones
Class III: Intracellular Signal Transducers
Class IV: Nuclear Transcription Factors
Class V: Cell-cycle Control Proteins
What is oncogenesis?
Unregulated proliferation of cellular growth due to mutations relaxing control of cellular growth
How do oncogenes cause oncogenesis?
They acts as dominant mutations at the cellular level, causing relaxation of cellular growth, allowing for unregulated proliferation
You would only need 1 mutation to be present on the alleles, hence it’s dominant
What are germline oncogenes?
- These are variant in cancer predisposition genes that are present in all of an infected individuals nucleic cells, as well as the cancer genome, and therefore may be inherited
- These account for about 5-10% of cancers, so most cancers are caused by somatic oncogenes
What are somatic oncogenes?
These are changes that have accumulated in the cancer genomes, either as drivers of oncogenesis, or as passenger mutations, but they are not present constitutionally in an individual
What do tumour suppressor genes do?
- Protective genes, help control growth
- Most inherited cancer syndromes are due to mutations in tumour suppressor genes
- In these cases, on of the mutations is inherited and the second is somatic - this is why we tend to earlier onset of cancers
How do tumour suppressor genes become inactivated?
- 2 mutations (one on each allele) cause inactivity of the tumour suppressor genes.
- Hence, these mutations are recessive at cellular level
What is Knudson’s two-hit hypothesis of sporadic and hereditary cancer?
Sporadic (not inherited):
- Single tumour
- Unilateral
- Late onset
1 - Fertilised egg inherits no mutation
2 - Mutation in one copy of gene occasionally occurs as cells divide (First hit)
3 - Mutation in second copy of gene occurs (Second hit)
Hereditary (inherited):
- Multiple tumours
- Bilateral
- Early onset
1 - Fertilised egg has 50% chance of inheriting mutation
2 - Mutation in one copy of gene is inherited in all body cells
3 - Mutation in second copy of gene occurs
What do DNA repair genes do?
Repair damage sustained by DNA
How do mutations in DNA repair genes lead to oncogenesis?
Mutations in DNA repair genes = increased risk of mutations in oncogenes/tumour suppressor genes
What is epigenetics?
The study of changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence
- DNA methylation
- Histone modification
How do epigenetic mechanisms lead to oncogenesis?
Methylation at CpG islands (rich in repeat of CG bases consecutively together) means the gene is silenced as transcription factors are unable to bind
Transcription factors turn specific genes on or off, by binding to nearby DNA
What are the 4 treatment modalities when treating cancer?
- Drug therapy
- Chemotherapy
- Endocrine therapy
- Immunotherapy
- Cellular therapy
- Targeted therapy
- Surgery - Focuses on specific site of cancer (e.g. colorectal cancer)
- Radiotherapy - Uses radiation to destroy cancer cells
- Best supportive care (managing symptoms)
How can surgery be used to treat cancer?
- Management of primary tumour
- Removal of malignant disease with a clear margin of normal tissue
- Repair, reconstruction and restoration of normal function
- Staging
- Management of regional lymph nodes or metastases (secondary tumours)
- Removal of lymph nodes around cancer and organs cancer is affecting
- This can determine the number of affected lymph nodes, and staging of the disease, as can help determine treatment given to patient
- Sentinel lymph node biopsy - Inject radioactive dye and use probe to detect where dye has gone and see main lymph node(s) affected by cancer, and then during surgery, the lymph nodes stained by the radioactive dye can be removed
- Staging of disease
- Palliative surgery
- Tumour debulking (Prolong survival but not curative)
- Symptom control
- Tumour fungation (tumour breaks through skin)
- Relief of obstruction
- Fracture fixation
- Control haemorrhage
How is radiotherapy used to treat cancer?
- High energy X-rays or gamma rays - cause DNA damage and cell death by inducing apoptosis. Affects healthy cells, but these cells often have functioning repair mechanisms, and so recover
- Radical/Palliative
- Single dose (fraction) or multiple doses
- External beam
- Linear accelerator
- Moves person in 360 degree movements
- CT plan - CT scan used to make radiotherapy treatment plan
- Define treatment area
- Identify organs at risk
- Dose calculation
- Brachytherapy - Radiotherapy waves injected into tumour, release radiowaves that kill tumour
How is chemotherapy used to treat cancer and how does it work?
- Chemotherapy - Usually given by IV drip
- DNA damage- leads to double strand DNA breaks
- Inhibit mitosis
- Inhibit DNA replication
- Most effective against fast growing cancers
- High sensitivity - Leukaemia, lymphoma, germ cell tumours, small cell lung cancer
- Moderate sensitivity - Breast, colorectal, bladder ovarian and cervical cancers
- Low sensitivity - Prostate, kidney, primary brain tumours, melanoma - these respond better to targeted treatments
How is endocrine therapy used to treat cancer and how does it work?
- Used in hormone driven cancers
- Breast - Tamoxifen, Anastrazole
- Prostate - Zoladex, Enzalutamide
- Long term adjuvant therapy - can be used after curative surgery to prevent cancer recurring
- Prophylactic - Can be used to prevent cancer from occurring e.g. People with BRCA1 gene
How is immunotherapy used to treat cancer and how does it work?
Leverages body’s immune system to fight cancer by either boosting its ability to recognise and attack cancerous cells or by modifying its ability to target cancer cells more effectively
