Non-targeted cancer therapies

Question 1

Surgical oncology

Answer 1

Only curative if not metastatic
Removal of large intestine prevents Familial adenomatous polyposis
Mastectomy prevents breast cancer
Commonly used in combined therapy

Question 2

Fluorescence guided surgery

Answer 2

Enables location of tumour

Peptide with probe bound added. Digested by matrix metalloproteases (secreted by most cancers) to reveal fluorescence

Question 3

Radiotherapy

Answer 3

Can be used before (neoadjuvant) or after surgery (adjuvant)
Damages normal cells but cancer cells are more sensitive as dividing more rapidly and mutations in DNA repair

External beam therapy (photon/proton)
Brachytherapy
Systemic therapy

Question 4

Photon radiotherapy

Answer 4

X or gamma ray
Directly ionises DNA or induces free radicals from water.
Induction of DNA damage response leading to cell cycle arrest/DNA repair or apoptosis
Dose delivered as several alignments (damages surrounding tissue)

Question 5

Proton beam therapy

Answer 5

Causes direct and indirect DNA damage
Deposit energy in a specific area (Bragg point) reducing damage to surrounding tissue

So-far used to treat uveal melanoma

Question 6

Brachytherapy

Answer 6

Uveal melanoma

Radioactive plaque added to eye near tumour which releases radioactive dose

Question 7

Systemic therapy

Answer 7

Liquid drug taken by mouth or injection
Contains a radioactive isotope
Can be coupled to a monoclonal antibody to direct to tumour
Treats thyroid, bone and prostate cancers

Question 8

Radiotherapy resistance

Answer 8

Tissue specific gene expression
Deficient DNA repair mechanisms
Solid tumours often have hypoxic environment (failure to induce free radicals)

Question 9

When chemotherapy is used

Answer 9

Neoadjuvant to shrink a tumour before surgery or radiation
Adjuvant to kill remaining cells post surgery
Curative as a single therapy
Palliative for patients with advanced/metastatic cancer

Question 10

Chemotherapy

Answer 10

Disrupts cell proliferation
Most effective against rapidly dividing cells
Non-specific. Normal rapidly dividing cells are affected
Compromised renewal of epithelial barrier

Question 11

Anti-metabolites

Answer 11

Similar to naturally occurring compounds
Inhibit nucleic acid synthesis
S phase specific
Require active transport
Breast cancer, leukaemia, lung cancer

Question 12

Methotrexate

Answer 12

Antimetabolite
Analogue of folic acid
Inhibits dihydrofolate reductase
Blocks purine and pyrimidine nucleic acid synthesis in S-phase

Question 13

Anthracyclines

Answer 13

Intercalate into DNA in S and G2 phase
Doxorubicin inhibits Topoisomerase II (DNA correcting enzyme) preventing DNA replication

Breast, bladder and Acute lymphocytic leukaemia

Question 14

Microtubule binding agents

Answer 14

Complex organic bases
Natural and semi-synthetic
Microtubule destabilising drugs (Videsine)
Microtubule stabilising drugs (Taxol)
Result in mitotic arrest

Question 15

Taxol

Answer 15

Blocks disassembly of the mitotic spindle during cell division through stabilisation of microtubule polymer
Chromosomes unable to achieve metaphase spindle configuration

Breast, ovarian and lung cancer

Question 16

Alkylating agents

Answer 16

Add Alkyl groups to guanine bases.
Form interstrand and intrastrand crosslinks
Works particularly in S-phase
multiple severe side effects
Cyclophosphamide has bladder and renal toxicity

Question 17

Differentiation

Answer 17

Promyelocytes treated with all-trans retinoic acid to induce differentiation and form neutrophils

Treatment of acute promyelocytic leukaemia (APML)

Question 18

Gemcitabine

Answer 18

Converted to gemcitabine triphosphate (active form)
Intercalates into DNA
DNA polymerase stalls and unable to replicate DNA