PHARM Y1 S1: Anticancer drugs

Question 1

how to determine which chemotherapeutic drug will be picked

Answer 1

• take some tumour cells
• screen diff drugs to determine whether they’ll be effective

Question 2

examples of classic anticancer drugs

Answer 2

• alkylating agents + platinum compounds
• cytotoxic antibiotics
• anti-metabolites
• plant alkaloids
• hormonal antagonists (breast and prostate cancer) and glucocorticoids (blood cancers)

Question 3

alkylating agents + platinum compounds

Answer 3

• insert alkyl group into DNA
• creates covalent cross-links b/n diagonal guanines on opposite strands > stress on DNA > apoptosis
• can work @ any part of cell cycle (non-specific)
• e.g. cyclophosphamide
• platinum compounds end in -platin e.g. cisplatin

Question 4

cytotoxic antibiotics + example

Answer 4

• inhibit transcription + translation (G1 and G2)
• can also inhibit topoisomerase - DNA replication (S)
• too many side effects as a regular antibiotic so used for cancer
• e.g. doxorubicin

Question 5

anti-metabolites

Answer 5

• substitute themselves into DNA replication pathway (S-phase)
• e.g. methotrexate (folate antagonist) and fluorouracil

Question 6

plant alkaloids

Answer 6

• mitotic poisons: vinca alkaloids and taxanes: inhibit spindle formation (mitosis)
• topoisomerase inhibitors (S-phase)

Question 7

how do hormonal antagonists work for breast cancer + give 2 examples

Answer 7

• selective oestrogen receptor modulator: tamoxifen: oestrogen receptor antagonist in the breast, inhibiting breast cancer growth - G1
• anastrozole: inhibits aromatase which inhibits oestrogen production - G1

Question 8

how do glucocorticoids work and give an example

Answer 8

• cause apoptosis
• most effective in blood borne cancers b/c they target lymphocytes
• prednisolone

Question 9

how do hormonal antagonists work for prostate cancer + give 2 examples

Answer 9

• anti-androgens: bicalutamide: inhibit activity of androgens (class of hormones which includes testosterone) - G1 phase
• gonadotropin-releasing hormone (GnRH) analogues: competitively inhibits actions of GnRH, preventing sex hormone secretion

Question 10

common symptoms of anticancer drugs

Answer 10

• target rapidly proliferating cells, therefore:
• hair loss
• mouth + GIT inflammation
• skin blistering + necrosis
• infertility
• N&V

Question 11

novel anticancer drugs

Answer 11

• monoclonal antibodies
• immune therapy: interferons, interleukin 2 and checkpoint inhibitors
• protein kinase inhibitors

Question 12

what is a mAb + 2 e.g.s

Answer 12

• react w/ specific target proteins on cancer cell
• can attach to + inactivate growth factor receptors on cancer cells > apoptosis
• can also attach a cytotoxic drug to the mAb which kills cancer cells
• trastuzumab: targets HER-2 receptors in breast cancer > increased immune response
• rituximab: binds to CD20 receptor on B cells in non-Hodgkin’s lymphoma > cell lysis

Question 13

immune therapy

Answer 13

• boost own immune system to help it fight cancer
• cytokines: interferons + interleukin 2
• checkpoint inhibitors

Question 14

what do interferons do

Answer 14

• secreted by monocytes
• increase cytotoxicity of NK cells, T cells + macrophages to kill cancer cells

Question 15

what does interleukin-2 do

Answer 15

• secreted by CD4+ T cells
• causes increased proliferation of CD8+ T cells to be able to kill cancer cells by causing apoptosis

Question 16

checkpoint inhibitors

Answer 16

• T cells contains proteins which stop the immune response (CTLA-4 and PD-1)
• checkpoint inhibitors inhibit these proteins to switch T cell function back on

Question 17

protein kinase inhibitor

Answer 17

• inhibit protein kinases (e.g. tyrosine kinase) which are essential for cancer cell division
• restricted to leukaemia + GIT tumours
• some also inhibit angiogenesis
• suffix -inib

Question 18

effect of anticancer drugs on organs

Answer 18

• heart: dysrhythmias
• lungs: toxicity
• renal failure
• nervous system: paraesthesia
• bladder: bleeding + inflammation

Question 19

how to manage adverse effects of anticancer drugs

Answer 19

• analgesics
• antidepressants
• antiemetics (setrons) to prevent N&V
• colony stimulating factors (CSFs) e.g. erythropoietin or filigrastim (stimulate WBCs)

Question 20

main complications w/ anticancer agents

Answer 20

• drug resistance by tumour
• tumour sanctuary: tumour cells grow in compartments inaccessible to drugs > creates relapse sites e.g. many drugs can’t cross BBB
• dose exhaustion: maximum dose combined w/ Pt’s immune system is still not enough to attack remaining cancer

Question 21

how to overcome drug resistance

Answer 21

• use multiple cytotoxic drugs w/ diff mechanisms of action
• ‘drug holiday’ (take a break from drugs): cells may become more susceptible to drug

Question 22

how to overcome tumour sanctuary

Answer 22

• treat w/ radiotherapy or surgery

Question 23

how to overcome dose exhaustion

Answer 23

• use multiple cytotoxic drugs w/ diff mechanisms of action
• combine w/ radiotherapy/surgery

Question 24

sensitising agents

Answer 24

• makes cells on outside of tumour more recognisable to immune system
• must be applied repeatedly as they only address the superficial layer of cells