(SYNOPTIC) Cancer - Cancer Recap Flashcards
What does the ‘pathobiology’ of cancer refer to?
How a cancer cell forms
Define cancer
A collection of diseases with the shared underlying features of uncontrolled cell growth and invasion
How are cancer cells formed?
Cancer cells are formed when normal cells undergo specific changes that allow them to proliferate without normal limit and spread to surrounding and/or distant tissues (multiple changes are usually required)
What influences cancer progression?
- Inherited susceptibility
- Lifestyle (e.g. smoking)
What are the 6 hallmarks of cancer and why are they important?
- Gain growth factor independence
- Insensitivity to growth inhibitors
- Proliferate without limit
- Avoid apoptosis
- Promote angiogenesis
- Invade and metastasise
These hallmarks are key to understanding how cancer cells grow and spread
What causes cancer?
A single cell has to be able to acquire (usually after multiple mutations) most or all of the hallmarks in order to progress to cancer, which takes time
Why is cancer more prevalent in older people?
Developing enough mutations to progress to a cancerous cell takes time as it requires multiple mutations to achieve most/ all hallmarks
What are the aims/priorities in management of cancer?
(1) Prevention
(2) Early detection
(3) Total eradication
When therapy is initiated, there must be a realistic assessment of the cancer management programme
What is the hierarchy of aims in cancer management?
- Cure - eradication of tumour and metastasis
- Remission/Mitigation - significant reduction in tumour load (increased survival)
- Symptomatic/Palliation - treatment of secondary complications (relief of symptoms)
- Terminal care - improve quality of life (optimise symptom control)
What are the main modes of therapy in cancer?
(1) Surgery
(2) Chemotherapy
(3) Radiotherapy
When would surgery be considered as an appropriate mode of therapy in cancer treatment?
- well-defined solid tumour
- non-vital region (e.g. mastectomy)
- non-mutilating result
- resection/reconstruction possible (e.g. gut)
When would radiotherapy be considered as an appropriate mode of therapy in cancer treatment?
- diffuse but localized tumour (e.g. lymphoma)
- vital organ/region (e.g. head and neck, CNS)
- adjuvant therapy (e.g. post mastectomy)
- palliation
When would chemotherapy be considered as an appropriate mode of therapy in cancer treatment?
- adjuvant therapy following surgery or radiotherapy
- neo-adjuvant therapy prior to surgery or radiotherapy
- widely disseminated/metastasized
- diffuse tumour (e.g. leukaemia)
- palliation
- some primary tumours(e.g. Hodgkin’s lymphoma)
What is the rationale of chemotherapy?
Target cancerous cells during rapid proliferation
What factors determine the growth of a tumour?
- cell cycle time
- growth fraction
- number of cells
When are chemotherapeutic agents least effective?
by the time tumours are clinically apparent (around 109 cells or more) most tumours are in the relatively slow phase of growth and therefore chemotherapy is less effective
What should be considered when using chemotherapeutic agents in combination?
the combination of drugs chosen should have minimal overlap toxicity
How should chemotherapy treatment be delivered and why?
Treatment should be delivered on an intermittent basis with the shortest possible time between treatments that allows recovery of the most sensitive normal tissue (e.g. bone marrow or gut)
This is to allow enough time for normal healthy cells (e.g. bone marrow) to recover but not enough enough time for cancer cells to recover by the time we go into cell cycle 2
Why should chemotherapy be delivered intermittently?
To allow for recovery of most sensitive tissues
- Rapidly dividing, e.g. bone marrow/ gut mucosa/ hair follicles
What are some examples of rapidly dividing cells in the body?
(1) White blood cells (bone marrow)
(2) Gut mucosa
(3) Hair follicles
What are the different phases of the cell cycle and how long does each phase last for?
- G1 phase - Synthesis of component of DNA (5 hours)
- S phase - DNA synthesis (7 hours)
- G2 phase - Synthesis of components for cell division (3 hours)
- M phase - Cell division (1 hour)
Which phase do anti-metabolites target in the cell cycle and give an example?
G1 Phase
E.g. Methotrexate
- Prevent synthesis of components of DNA
Which phase do microtubule inhibitors target in the cell cycle and give an example?
G2 Phase
E.g. Vinca alkaloids (Vinblastine, Vincristine, Docetaxol)
- Prevent cells making components needed to separate
Which phase do agents binding to DNA target in the cell cycle and give an example?
S Phase
E.g. Alkylating agents, Anti-tumour antibiotics, Platinum compounds, Miscellaneous others
- Prevent DNA synthesis
What are the benefits of using combined chemotherapeutic agents over single chemotherapeutic agents?
Combination therapy led to increased remission, in terms of both patient numbers and length of remission time
What are the drawbacks of using combined chemotherapeutic agents over single chemotherapeutic agents?
More aggressive regimen results in increased side effects
What causes side effects experienced in chemotherapy?
Mechanism of action of conventional chemotherapy drugs:
- cancer cell are rapidly dividing
- chemotherapy drugs target rapidly dividing cells
- most chemotherapy drugs are non-selective for cancer cells, therefore impacting other rapidly dividing cells causing side effects (e.g. targeting hair follicle cells leading to hair loss)
What are the aims to minimise side effects in chemotherapy?
- reduce discomfort, morbidity and mortality
- increase the tolerable dose threshold and thus the dose that can be used
- Close monitoring
- Prevention is used wherever possible
What is specifically monitored in chemotherapy?
Full blood counts
Give examples of how prevention of side effects is used in chemotherapy?
- by allowing adequate time for marrow recovery between treatments, or by administering stem cell growth factors with chemotherapy to selectively enhance marrow proliferations
- forced diuresis is now routinely given with nephrotoxic and bladder toxic drugs to reduce contact time and urine concentration. This involves modest over-hydration before therapy followed by a diuretic to maintain a high urine output for at least 24 hours following therapy (e.g. Mannitol)
