Chemotherapy, Targeted Therapy and immunotherapy

Question 1

Describe the aim of chemotherapy

Answer 1

The aim of chemotherapy is to cause as much damage as possible to force cells into apoptosis (by targeting DNA, RNA and proteins).

Question 2

Describe the precautions took in delivery of chemotherapy

Answer 2

• IV and oral preparations
• Frequency of administration = cycles
• (cycles are determined by pharmokinetics - half life e.g)
• Combination chemotherapy has a greater efficacy

Question 3

List the three settings in which chemotherapy can be given.

Answer 3

• Neoadjuvant - before surgery, with the aim to reduce the size of cancer
• Adjuvant - to reduce the risk of cancer returning.
• Palliative - to control disease for as long as possible.

Question 4

Name the three main types of chemotherapy

Answer 4

1. Alkylating agents and platinum drugs
2. Antimetabolites
3. Organic drugs

Question 5

Describe alkylating agents and platinum drugs.

Answer 5

This type of chemotherapy forms DNA adducts and blocks DNA replication (all phases of the cell cycle).

Question 6

Describe organic drugs (as chemotherapy)

Answer 6

• Vinca alkaloids - bind to tubulin and prevent microtubule assembly
• taxanes - bind to beta tubulin subunit inhibiting depolymerisation and disrupting mitotic spindle
• anthracyclines - microbial antibiotic targets topoisomerase 2.

Question 7

Describe antimetabolites

Answer 7

Structurally mimic essential molecules required for cell division (S phase of cell cycle).

Question 8

List some side effects of chemotherapy

Answer 8

Mucositis
Alopecia
Pulmonary fibrosis
Neuropathy
Sterility
Nausea/vomiting
etc, etc.
chemo therapy affects quality of life

Question 9

Name some personalised systemic therapies.

used in combating cancer

Answer 9

• Hormonal therapies - anti -oestrogen, aromatase inhibitors.
• Targeted therapies - EGFR, VEGF, CDK 4/6
• Immunotherapy - PD 1, PD -L1, CTLA -4

Question 10

Descrbe hormonal therapy in breast cancer.

Answer 10

Oestrogens play a major role in breast cancer, they promote cell proliferation in the breast tissue (higher rate of cell division = more chances for mutations).
So anti-oestrogen drugs (tamoxifen - contraceptive pill) binds to the oestrogen receptor, therefore blocking the oestrogen induced proliferation of cells in the breast tissue.

Question 11

Describe targeted treatment in terms of EGF

Answer 11

EGF = epidermal growth factor.
(similar to VEGF)
EGF binds to the tyrosine kinase receptor on the membrane, leading to receptor dimerisation and autophosphorylation.
Following this is the activation of signal transduction pathways (incl. RAS and transcription = gene expression and growth).

Question 12

Describe the involvement of CDK 4/6 inhibitors in cancers.

Answer 12

CDK 4/6 = cyclin dependant kinase inhibitors.
Cyclins and cyclin dependent kinases control the passage of cells through each phase of the cell cycle.

The inhibitors block the progression of cells through the cell cycle.

Question 13

Describe the role of the immune system in targeting cancer.

Answer 13

B cells - produce tumour specific antibodies
T cells - helper T cells vs cytotoxic T cells = kill the virus.

Question 14

Describe immune checkpoints.

Answer 14

Immune checkpoints ensure that self tolerance is maintained.
Activated by receptor ligand binding to (PD-1 to PD-L1) (CTLA - 4 to B7)
(immune checkpoint inhibitors - removal of the brakes of the immune system allowing increased T cell activity)

Question 15

Describe pembrolizumas as a therapeutic agent.

Answer 15

IgG4 monoclonal antibody.
Targeted at PD-1 checkpoint blocking binding to PD-L1 and PD-L2 on tumour.
As a result, T cells are activated and can attack tumour cells.

Question 16

List some side effects of immunotherapy.

Answer 16

Colitis
Pneumonitis
Hypophysitis
Dermatitis
Nephritic
Neurological