6 Causes, prevention and treatment of cancer

Question 1

List some common causes of cancer

Answer 1

• Carcinogens
• Infectious agents
• Inherited predisposition

Question 2

Explain how carcinogen cause mutations

Answer 2

• Reaction with free radicals (radiation)
• Mechanisms include adducts, cross links, breaks etc.
• Increases the rate of mutation, DNA breaks or base changes
• Leads to errors such as incorrect bases incorporated or mis-joining of chromosome ends

Carcinogens cause damage. Repair caused mutations

Question 3

Describe how infectious agents cause cancer

Answer 3

Mechanisms:
1. Inflammation - cure with abs
2. Inflammation and genes
 > acute = hepatitis
 > chronic = cancer
3. Oncogenes - vaccination
4. Oncogenes - glandular fever + cancer
5. Immune suppression - control with antivirals

Question 4

Describe some other mechanisms by which infectious agents can cause cancer

Answer 4

Inflammation

• viruses
• also, asbestos [chronic inflammation in lungs] = (mesothelioma)

Immune suppression
- Immune suppression leads to small increase in cancer frequency (especially virally induced cancers)

Individually small effects
- food types (processed), chemical exposure, alcohol, obesity

Intrinsic causes

• Tissue growth (developmental)
• Hormones (breast + prostate)

Question 5

Describe the principle behind inherited cancer predispositions

Answer 5

• An inherited mutation in a gene that causes a defect in machinery that guards against DNA damage (other monitoring or DNA repair)
  e. g. Li-Fraumeni syndrome (p53; multiple cancers), or BRCA1 (breast cancer)

Question 6

Describe cancer predisposition in the general population

Answer 6

We all carry some sort of genetic predisposition to cancer

- But almost all have genetic resistance to cancer

Question 7

What sort of genes affect probability of developing cancer?

Answer 7

e.g. GST (glutathione transferases) - protects cells against oxidative stress and several toxic molecules - GST gene polymorphisms as factors modulating the risk of developing cancer

Question 8

List some common cancer screening programmes

Answer 8

UK programmes:

• Breast
• Cervical
• Colon
• Prostate

Question 9

Describe how genetics is used in cancer screening, using BRCA1 as an example

Answer 9

BRCA1

• Gene involved in breast and also ovarian cancers
• Women offered testing if known to be in a family or ethnic group with this predisposition
• If a mutated BRCA1 gene is found, then they are offered a mastectomy

Family with known genetic inheritance also screened for colon, kidney, pancreatic cancers (requires that markers of genetic predisposition are known)

Question 10

Describe how the breast cancer screening programme works

Answer 10

Breast cancer
- X-ray based mammography from 1970-80’s saves around 1,400 lives per year in the UK
- However, any would not progress to a life-threatening cancer (not aggressive/death)
- Estimated 3 cases over-diagnosed for every life saved
> i.e. there is 1/200 chance screening will save a women’s life but a 3/200 chance that treatment will be unnecessary

Question 11

Describe how the cervical cancer screening programme works

Answer 11

Cervical Cancer

• offered to 25 year olds+
• Pap smear replaces liquid-based cytology (LBC) plus HBC assay
• Pap smear works well as normal cells of cervix are relatively uniform
• UK mortality now ~70% lower than 30 years ago

Question 12

Describe how the bowel cancer screening programme works

Answer 12

• Over 16,000 deaths/year in UK
• Generally, starts as a slow growing precancerous mass
• Tests include faecal occult blood test (FOBT) in UK, and colonoscopy
• Colonoscopy shown to detect 4-5x more polyps and cancers that FOBT, but 10x the const
• Virrtual colonoscopy (CAT scan) gives 3D picture of colon and rectum

Question 13

List some common cancer therapeutics

Answer 13

• Surgery
• Radiotherapy
• Chemotherapy
• Targeted therapy

Question 14

Briefly describe how radiotherapy is used

Answer 14

Radiation therapy is a type of cancer treatment that uses beams of intense energy to kill cancer cells

• It most often uses X-rays
• Damages cells to such an extent that they cannot survive (cancer cells more sensitive to DNA damage)

Question 15

Briefly explain the mechanism of how radiotherapy works

Answer 15

Mitotic catastrophe

• Most dividing cancer cells initially survive, they continue to progress through the cell cycle despite the break in their DNA
• The genome becomes progressively more damaged until it is insufficiently intact to continue, and the cells die from ‘mitotic catastrophe’

Free radicals can also damage other components of the cell, such as membrane proteins which can then trigger apoptosis in an alternative pathway

Question 16

Describe the MOA of antimetabolites, with an example

Answer 16

E.g. Methotrexate

MOA: various, generally, interfere with DNA replication

Question 17

Describe the MOA of alkylating agents, with an example

Answer 17

E.g. Cyclophosphamide

MOA: DNA crosslinking

Question 18

Describe the MOA of platinum compounds, with an example

Answer 18

E.g. Cisplatin

MOA: Inhibit DNA synthesis

Question 19

Describe the MOA of Anthracycline antibiotics, with an example

Answer 19

E.g. Doxorubicin

MOA: DNA intercalation

Question 20

Describe the MOA of Topoisomerase inhibitors, with an example

Answer 20

E.g. Etoposide

MOA: Prevents ligation step

Question 21

Describe the MOA of Microtubule inhibitors, with an example

Answer 21

E.g. Paclitaxel

MOA: Variously stabilise or destabilise spindle

Question 22

List some other targeted therapies for cancer treatment

Answer 22

Antibodies to specific antigen
- e.g. Trastuzumab targets EGFR (HER2) mutants in breast cancer

Small molecule inhibitors

• e.g. Imatininb (a bcl-abl TK inhibitor in leukaemia)
• e.g. Vermurafenib blocks mutant B-raf in melanoma

Angiogenesis inhibitors
- e.g. Bevacizumab blocks VEGF in colon cancer

Immune system booster
- e.g. Vaccines

Question 23

Describe some cancer prevention methods

Answer 23

• Modify lifestyle: reduce smoking, avoid UV exposure, healthier diet (no processed meat)
• Immunisation: HPV, hepatitis
• Prenatal genetic diagnosis