0429 - Cancer Therapies

Question 1

What are the three possible goeals of cancer therapy?

Answer 1

Radical (curative)
Adjuvant
Palliative

Question 2

What are the five major forms of cancer therapy?

Answer 2

Surgery - Remove known masses.
Radiation - Kill cells locally
Hormonal - Inhibit growth and survival of hormone-dependent cells
Chemo - kill cells systemically
Targeted - Target specific cell growth processes.

Question 3

Briefly outline chemotherapy

Answer 3

Kills rapidly dividing cells, while allowing healthy tissue to recover before the next cycle. Works best with fewer cells (e.g. after surgery) as an adjuvant therapy.

Question 4

What are some ways of overcoming chemotherapy resistance?

Answer 4

Combination therapy - multiple drugs used at maximum doses
Dosage intensification - (e.g. prior to stem cell transplant)
Maintenance strategies
Target resistance mechanisms
New agents

Question 5

What are the advantages of targeted therapy for cancer?

Answer 5

Selective for the tumour cells
Fewer systemic toxicities
Dosing can be adjusted to the biologic activity of the drug.

Question 6

What are the two forms of targeted therapy for cancer?

Answer 6

Monoclonal Antibodies (mabs) - antibodies synthesised to bind to specific tumour markers or receptors required for growth, and neutralise their action.
Small molecule inhibitors (nibs) - Block the activity of signal pathways to prevent tumour cell growth.

Question 7

What is Her2 and how can it be used as a treatment target?

Answer 7

Human Epidermal Growth Factor Receptor 2 (also ErbB2)
A receptor that is overexpressed or mutated in 25% of breast cancers. Promotes invasion, survival, and angiogenesis.
Can be targeted by Trastuzumab (Herceptin) - blocks ligand binding or dimerisation, or lapatinib (Tykerb), inhibits the kinase, blocking signalling pathway. Trastuzumab is first choice of agent.

Question 8

What is VEGF and how can it be used as a treatment target?

Answer 8

Vascular Endothelial Growth Factor - key mediator of angiogenesis.
Bevacizumab (Avastin)
Tumour secretes VEGF to promote angiogenesis, Avastin binds to VEGF, preventing it from reaching the receptor.

Question 9

What is EGFR and how can it be used as a treatment target?

Answer 9

Epithelial growth factor receptor - regulates cell cycle progression, repair, and survival, and involved in metastasis. Often overexpressed in tumours.
Cetuximab (Erbitux) can bind to EGFR, preventing signalling.
In bowel cancer, requires the KRAS to be wild-type to be of benefit.
Can also use tyrosine kinase inhibitors - Gefitinib (Iressa), Erlotinib (Tarceva), Afatinib (Giotrif)