Session 7 - Cancer and the Cell Cycle

Question 1

What are four different ways in which cancer can spread?

Answer 1

Local - Direct involvemnt of surrounding structures
Lymphatic
Blood
Implantation

Question 2

What cancers spread via lymphatics?

Answer 2

Carcinomas and melanomas

Question 3

What cancers spread via the blood

Answer 3

Sarcomas and Carcinomas

Question 4

What cancers spread via implantation

Answer 4

Mechanical dump of tumour clump in peritoneum, ureters, CSF

Question 5

What are two synonyms for primary therapy?

Answer 5

Curative treatment

Radical treatment

Question 6

What is adjuvant chemotherapy?

Answer 6

Post-operativ treatment in a patient at high risk of microscopic metastases after removal of the primary tumour

Question 7

What is neoadjuvant chemotherapy?

Answer 7

Primary treatment of patients with a clinically localised tumour. Can be used ot asses biological responsiveness of tumour and to reduce size for surgery.

Question 8

What is always aimed for in neoadjuvant therapy?

Answer 8

PCR (pathological complete response)

Question 9

What is palliative chemotherapy?

Answer 9

Not curative, symptomatic treatment only

Question 10

In what malignancies is chemotherapy curative?

Answer 10

Haematological malignancies

Testicular cancr

Question 11

What is fractional chemotherapy?

Answer 11

hemotherapy is used in very narrow range to kill cells in a fractional way. This means that chemo given in bursts with intervals, allowing healthy cell populations (bone marrow, etc) to recover while hammering down the malignant, poorly corrective cancer cells.

Question 12

Give three types of cytotoxic agent?

Answer 12

Platinum compound
Anti-metabolites
Spindle Poisons

Question 13

What do platinum compounds do?

Answer 13

Inhibit DNA synthesis via formation of platinated inter- and intrastrand adducts leading to inhibition of DNA synthesis

Question 14

Name two anti-metabolites

Answer 14

Methotrexate

5-fluorouracil

Question 15

What does methotrexate do?

Answer 15

Inhibits dihydrofolate reductase

Question 16

What does 5-fluorouracial do?

Answer 16

Inhibits thymidylate synthase

Question 17

What do spindle poisons do?

Answer 17

Once chromosomes aligned at metaphase plate, spindle microtubules depolymerize, moving sister chromatids towards opposite poles. Nuclear membrane re-forms and cytoplasm divides.

Question 18

How do microtubule binding agents, such as spindle poisons, affect microtubule dynamics

Answer 18

Inhibit polymerization

Stimulate polymerization and prevent depolymerization

Question 19

What is the aim of combination therapy?

Answer 19

Activity vs safety

Question 20

Give two reasons to suggest why you would have two separate pharmacological agents in chemotherapy?

Answer 20

• Different mechanisms of action
• Different mechanisms of resistance
  However, must take into account compatability of side-effects

Question 21

Give a hormonal treatment in breast cancer other than tamoxifen

Answer 21

Aromatase inhibitors prevents Oestrogen conversion in fat from androgens – only work in post-menopausal women, as pre’s have functioning ovaries which will replace Oestrogen.

Question 22

What is arbiaterone?

Answer 22

A drug which inhibits enzyme CYP17A1, which is crucial in conversion of pregnenolone and progesterone to testosterone

Question 23

Name a drug which inhibits CYP17A1 and what is it used for?

Answer 23

Prostate cancer

Abiraterone

Question 24

In what ways doe a cnacer cell differ from a normal cell?

Answer 24

• Lose contact inhibition
• Increase in growth factor secretion
• Increase in oncogene expression
• Loss of tumour suppressor genes

Question 25

In what way do normal cells differ from cancer cells?

Answer 25

• Oncogene expression rare
• Intermittent or coordinated growth factor secretion
• Presence of tumour suppressor genes

Question 26

Give an example of biologically targeted therapy

Answer 26

Philadelphia chromosome of chonic myeloid leukaemia

Question 27

What is the philadelphia chromosome and what does it do?

Answer 27

• translocation of part of chromosome 9 to 22
• abl oncogene on 9 adjacent to breakpoint cluster bcr gene on 22, fusion leads to transcription of a protein and leukaemic transformation
• Provides target for anti-cancer therapy eg. STI 571

Question 28

Give a treatment for CML?

Answer 28

Imatinib, Bcr-Abl tyrosine kinase inhibitor targets Philadelphia cells in CML and has massively increased survivability.

Question 29

Give an antibody treatment for breast cancer

Answer 29

• Trastuzumab is a recombinant humanised IgG1 monoclonal antibody against the human
• epidermal growth factor receptor 2 (HER2).
• Antibody dependent cell mediated cytotoxicity (ADCC)

Question 30

Give a biological therapy for colon cancer

Answer 30

Erbitux, an IgG antiboyd targets extracellular EGFR, altering signalling cascade

Question 31

What is a VEGF trap?

Answer 31

Abflibercept – VEGF trap
VEGF romotes angiogenesis in vivo by inducing endothelial cells to invade collagen gels and proliferate to form capillary-like structures. The trap binds to VEGF and inhibits it.