Chemotherapy and other non-targeted treatments

Question 1

Surgery and radiotherapy for cancer

Answer 1

Surgery is best treatment for removal of solid tumour. Can be used for prevention by removal of precancerous tissue. Can also be used to improve likelihood of chemo working

Radio therapy can be external beam, or internal brachytherapy.

External beam projects high energy ionising radiation on the outside of the body at the region affected. Commonly used in cancer

Internal brachytherapy plants a radioactive seed within the body.

Question 2

Cell cycle overview

Answer 2

G1, S, G2, and M phases: drugs target M or S

S is chromosome duplication

M is mitosis.

Question 3

Downsides of chemo

Answer 3

Targets rapidly replicating cells, including normal cells such as hair follicles, bone marrow, GIT.

Can cause several toxicities such as neutropenia, anaemia, and thrombocytopenia.

Nausea, diarrhoea, mucositis, and alopecia common.

Can cause nephro- neuro- and cardiotoxicity.

Question 4

Alkylating-like agents mechanism and adverse effects

Answer 4

E.g., cisplatin

Platinum atom binds with genomic DNA (A and G bases) to create lesions (forms inter and intracrosslinks) which contort the DNA. This blocks DNA repair, synthesis and replication.

This affects the S cycle of the cell cycle -> G2 arrest

Used for wide range of cancers

Can cause nephrotoxicity (due to renal excretion being primary mechanism), hepatotoxicity (oxidative stress mediated), and GIT toxicity

Question 5

Antimetabolites mechanism and adverse effects

Answer 5

e.g., methotrexate, 5-fluoruracil

Folic acid’s metabolite tetrahydrofolate is essential for DNA synthesis and repair.

Methotrexate is an analogue of folic acid, and interferes in its metabolism by competitively inhibiting dihydrofolate reductase (DHFR), preventing the formation of tetrahydrofolate.

Blocks S phase of cell cycle.

Commonly used for leukaemia, lymphoma, and solid tumours.

Can cause nephrotoxicity, hepatotoxicity, pulmonary damage, mucositis, and neurotoxicity (demyelination mechanism)

Question 6

Topoisomerase Inhibitors mechanism and adverse effects

Answer 6

Topotecan is a topoisomerase I inhibitor.

Doxorubicin is a topoisomerase II inhibitor.

Topoisomerase enzymes regulate DNA supercoiling, with topoisomerase I causing single strand breaks, and topoisomerase II causing double strand breaks.

Both drugs inhibit the synthesis of DNA and interfere with the DNA structure.

Treat a wide range of cancers

Topotecan commonly causes myelosuppression

Doxorubicin commonly causes cardiotoxicity.

Question 7

Microtubule poisons mechanism and adverse effects

Answer 7

e.g., vincristine, vinblastine

Treats acute lymphoblastic leukaemia.

Binds to tubulin and prevents polymerisation. This inhibits cell division (M phase of cell cycle)

Can cause cardiotoxicity, peripheral neuropathy (motor nerve damage), and GIT issues.