Chemotherapy

Question 1

What are the 4 types of chemotherapy

Answer 1

Neo-adjuvant - given before surgery to reduce tumour size
Adjuvant - Chemotherapy given to destroy left-over (microscopic) cells that may be present after the known tumor is removed by surgery.
Palliative
Immunotherapy

Question 2

Why is chemotherapy given in 3 week cycles

Answer 2

To allow bone marrow cells to recover - they are also targeted as they are rapidly dividing

Question 3

Antimetabolites - describe their action , give an example

Answer 3

Interfere with metabolic pathways in DNA synthesis

Folate antagonist - prevent synthesis of nucleotides

Question 4

False substrates mechanism of action

Answer 4

Pyrimidine analogues
Inhibits thymidylate synthase
Incorporated into DNA leading to damage of DNA = cell dies

Question 5

Alkylating agents - mechanism of action

Answer 5

More side effects

Causing cross linking of DNA via alkylation = DNA cannot unwind = defective DNA replication

Question 6

Platinum chemotherapy - mechanism of action; main side effect

Answer 6

Inhibition of DNA synthesis by cross-linking guanine residues (prevent helix from unwinding )

Nausea with use is very common

Question 7

Anthracycline antibiotics - mechanism of action; adverse effect

Answer 7

intercalation (slotting between) DNA strands –> inhibition of topoisomerase (involved in uncoiling of DNA) + free radical generation –> inhibition of DNA synthesis

Cardio toxicity is a side effect

Question 8

Topoisomerase II inhibitors

Answer 8

Inhibition of topoisomerase II presents ligation of DNA leading to breaks in DNA

Question 9

Microtubule inhibitors

Answer 9

Vinca alkaloids block the formation of mitotic spindle - required for mitosis
Taxanes stabilise spindle fibres - this prevents the migration of chromosomes during anaphase

Question 10

Side effects of chemotherapy

Answer 10

Inhibit growth of gut epithelia and hair loss

Myelosuppression can lead to anaemia and low neutrophil counts (neutropenic sepsis due to decreased resistance to infection)

Infertility

Cardio toxicity - damage to heart muscle resulting in impaired heart activity (SoB, chest pain, peripheral oedema, palpitations and dizziness)

Question 11

Treating side effects if chemotherapy

Answer 11

Colony stimulating factors to increase WBC count

Prevent infections with antibiotics and anti fungal

Question 12

Describe the principle of targeted anticancer therapy.

Answer 12

Exploits faulty genes/signalling pathways/tumour growth/angiogenesis
Hormonal targets
Molecular testing to determine receptor expression

Question 13

Describe the relevance of human epidermal growth factor receptor-2 as a target in anti-cancer treatment.

Answer 13

Naturally present in low levels but over expressed in some cancers, breast cancer most commonly

Due to oncogene activation

Affects gene transcription and cell cycle

Question 14

Describe the role of tyrosine kinase inhibitors in anticancer treatment. identify the two cancer they usually used for

Answer 14

Tyrosine kinase leads to uncontrolled cell proliferation
Imatinib inhibits TK activity
Selective inhibitor very effective for Chronic Myeloid Leukaemia
Also used for gastro-intestinal stroma tumours

Question 15

Describe the role of proteasome inhibitors in anticancer treatment.

Answer 15

Proteosomes: cellular structures which degrade proteins
Some proteins kill cancer cells: pro-apoptotic factors
Inhibition of intracellular proteasomes alters the regulation of intracellular proteins
eg bortezomib used in multiple myeloma

Question 16

Describe the role of anti-VEGF based drugs in anticancer treatment.

Answer 16

Vascular Endothelial Growth Factor
VEGF secreted to promote angiogenesis
Angiogenesis: blood vessel growth to support metastasis
Bevacizumab: monoclonal antibody
Advanced colonic and breast cancer
Sunitinib: inhibits VEGF-associated receptor tyrosine kinase
Advanced renal carcinoma

Question 17

Symptoms of ovarian cancer

Answer 17

Abdominal pain 
Persistent indigestion/nausea
Bloating
Pain during sex
Altered bowel habits
Back pain
Vaginal bleeding
Tired all of the time
Unintentional weight loss

Question 18

Tamoxifen - describe its mechanism of action

Answer 18

Blocks oestrogen as a selective estogen-receptor modulator (SERM)

Prevents breast cancer /reduces growth of breast cancer (must be ER +)

Also prevents bone loss

Question 19

Aromatase inhibitors

Answer 19

Androgens converted to oestrogens via aromatase in post-menopausal women
Oestrogens promote tumour growth in ER+ breast cancers

Question 20

what is the philadelphia chromosome? which cancer is it associated with?

Answer 20

An abnormality of chromosome 22 in which part of chromosome 9 is transferred to it; associated with Chronic Myeloid Leukaemia
produces bcr-abl protein which promotes tyrosine kinase activity

Question 21

Describe the epidermal growth factor (EGF receptor) kinase

Answer 21

they are a type of tyrosine kinase receptors

epidermal growth proteins are needed for cell signaling pathways that control cell division and survival

Question 22

PARP inhibitors - mechanism of action; which cancers are treated with them?

Answer 22

PARP is a DNA-repairing enzyme (single-strand break)
BRCA genes important in DNA repairs - if mutation occurs here = PARP inhibition = inability of cancer cells to repair double strand breaks=cell death
used for breast, prostate and ovarian cancer