(SYNOPTIC) Cancer - Cancer Recap

Question 1

What does the ‘pathobiology’ of cancer refer to?

Answer 1

How a cancer cell forms

Question 2

Define cancer

Answer 2

A collection of diseases with the shared underlying features of uncontrolled cell growth and invasion

Question 3

How are cancer cells formed?

Answer 3

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)

Question 4

What influences cancer progression?

Answer 4

• Inherited susceptibility
• Lifestyle (e.g. smoking)

Question 5

What are the 6 hallmarks of cancer and why are they important?

Answer 5

1. Gain growth factor independence
2. Insensitivity to growth inhibitors
3. Proliferate without limit
4. Avoid apoptosis
5. Promote angiogenesis
6. Invade and metastasise

These hallmarks are key to understanding how cancer cells grow and spread

Question 6

What causes cancer?

Answer 6

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

Question 7

Why is cancer more prevalent in older people?

Answer 7

Developing enough mutations to progress to a cancerous cell takes time as it requires multiple mutations to achieve most/ all hallmarks

Question 8

What are the aims/priorities in management of cancer?

Answer 8

(1) Prevention
(2) Early detection
(3) Total eradication

When therapy is initiated, there must be a realistic assessment of the cancer management programme

Question 9

What is the hierarchy of aims in cancer management?

Answer 9

1. Cure - eradication of tumour and metastasis
2. Remission/Mitigation - significant reduction in tumour load (increased survival)
3. Symptomatic/Palliation - treatment of secondary complications (relief of symptoms)
4. Terminal care - improve quality of life (optimise symptom control)

Question 10

What are the main modes of therapy in cancer?

Answer 10

(1) Surgery
(2) Chemotherapy
(3) Radiotherapy

Question 11

When would surgery be considered as an appropriate mode of therapy in cancer treatment?

Answer 11

• well-defined solid tumour
• non-vital region (e.g. mastectomy)
• non-mutilating result
• resection/reconstruction possible (e.g. gut)

Question 12

When would radiotherapy be considered as an appropriate mode of therapy in cancer treatment?

Answer 12

• diffuse but localized tumour (e.g. lymphoma)
• vital organ/region (e.g. head and neck, CNS)
• adjuvant therapy (e.g. post mastectomy)
• palliation

Question 13

When would chemotherapy be considered as an appropriate mode of therapy in cancer treatment?

Answer 13

• 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)

Question 14

What is the rationale of chemotherapy?

Answer 14

Target cancerous cells during rapid proliferation

Question 15

What factors determine the growth of a tumour?

Answer 15

• cell cycle time
• growth fraction
• number of cells

Question 16

When are chemotherapeutic agents least effective?

Answer 16

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

Question 17

What should be considered when using chemotherapeutic agents in combination?

Answer 17

the combination of drugs chosen should have minimal overlap toxicity

Question 18

How should chemotherapy treatment be delivered and why?

Answer 18

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

Question 19

Why should chemotherapy be delivered intermittently?

Answer 19

To allow for recovery of most sensitive tissues

- Rapidly dividing, e.g. bone marrow/ gut mucosa/ hair follicles

Question 20

What are some examples of rapidly dividing cells in the body?

Answer 20

(1) White blood cells (bone marrow)
(2) Gut mucosa
(3) Hair follicles

Question 21

What are the different phases of the cell cycle and how long does each phase last for?

Answer 21

• 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)

Question 22

Which phase do anti-metabolites target in the cell cycle and give an example?

Answer 22

G1 Phase

E.g. Methotrexate

- Prevent synthesis of components of DNA

Question 23

Which phase do microtubule inhibitors target in the cell cycle and give an example?

Answer 23

G2 Phase

E.g. Vinca alkaloids (Vinblastine, Vincristine, Docetaxol)

- Prevent cells making components needed to separate

Question 24

Which phase do agents binding to DNA target in the cell cycle and give an example?

Answer 24

S Phase

E.g. Alkylating agents, Anti-tumour antibiotics, Platinum compounds, Miscellaneous others

- Prevent DNA synthesis

Question 25

What are the benefits of using combined chemotherapeutic agents over single chemotherapeutic agents?

Answer 25

Combination therapy led to increased remission, in terms of both patient numbers and length of remission time

Question 26

What are the drawbacks of using combined chemotherapeutic agents over single chemotherapeutic agents?

Answer 26

More aggressive regimen results in increased side effects

Question 27

What causes side effects experienced in chemotherapy?

Answer 27

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)

Question 28

What are the aims to minimise side effects in chemotherapy?

Answer 28

• 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

Question 29

What is specifically monitored in chemotherapy?

Answer 29

Full blood counts

Question 30

Give examples of how prevention of side effects is used in chemotherapy?

Answer 30

• 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)