Chemotherapy & Immunotherapy

Question 1

how can chemotherapy be classified?

Answer 1

• Classification by cell cycle preference
• Classification by chemical properties

Question 2

what are the stages of the cell cycle and which stages to cell-cycle specific and non cell-cycle specific chemotherapy drugs act on?

Answer 2

G0 phase: Undivided cell

G1 phase: Duplication of cellular content. Cellular growth

S phase: DNA replication

G2 phase: Further cell growth

M phase: Cell division

cell cycle specific = G1, S, G2, M not G0

cell cycle non specific = all stages

Question 3

what are some classes of cell cycle specific chemotherapy drugs?

Answer 3

taxanes

vinca alkaloids

antimetabolites

topoisomerase inhibitors

Question 4

what are some classes of cell cycle non-specific chemotherapy drugs?

Answer 4

alkylating agents (busulfan, cyclophosphamide)

platinum analogs (carboplatin, cisplatin)

anthracyclines

Question 5

what are alkylating agents?

Answer 5

Bind covalently via alkyl groups to DNA making cross-linking between the DNA strands preventing the DNA from replication

Question 6

what are platinum agents?

Answer 6

They bind covalently to the DNA forming cross-links preventing the DNA from replication.

eg cisplatin, carboplatin, oxaliplatin

Question 7

what are antimetabolites?

Answer 7

They have a similar structure to normal metabolites which are required for DNA synthesis.

They affect DNA synthesis by acting as a substitute to the actual metabolites that would be used in the normal metabolism

Question 8

what are topisomerase inhibitors?

Answer 8

• Topoisomerase is an enzyme that cuts one or both straps of the DNA to prevent the overwinding during DNA replication.
  
  • Topoisomerase 1: cuts one strand of the DNA
  • Topoisomerase 2 : cuts both strands off the DNA

Question 9

what are tubulin active agents?

Answer 9

Bind to tubulin and prevent the formation of mitosis spindles which are crucial for chromosome separation during cell division.

eg

Vinca Alkaloids: Vinblastine, vincristine, vinorelbine

Taxanes: docetaxel, paclitaxel

Epothelones: Eribulin

Question 10

what are some immediate side effects of chemotherapy?

Answer 10

• extravasation - leakage of chemotherapy to the adjacent tissue
• facial/body flushing
• cardiac arrhythmias
• hypotension
• hypersensitivity
• anaphylaxis
• haemorrhagic cysts

Question 11

what are some short to medium term side effects of chemotherapy?

Answer 11

• Discoloration of urine
• Tumour lysis syndrome
• Nausea and vomiting
• Mucositis
• Constipation
• Diarrhoea
• Fatigue

Question 12

what are some medium to long term side effects of chemotherapy?

Answer 12

• Bone Marrow suppression
• Alopecia
• Liver dysfunction
• Renal toxicity
• Cardiac toxicity
• Peripheral neuropathy
• Pulmonary Fibrosis
• Changes in fertility

Question 13

describe how chemotherapy can become resistant

Answer 13

Cancer cell can develop many resistance mechanisms to chemotherapy drugs:

1. Cancer cells limit chemotherapy drugs accumulation by modifying their membrane composition.
2. Reducing drug transporters
3. Increasing efflux pumps
4. Developing detoxification mechanisms lead to drug inactivation
5. Drug target modification or loss
6. Sophisticated DNA repair system and upregulation of prosurvival genes

Question 14

what are the 5 categories of immunotherapy?

Answer 14

1. Checkpoint inhibitors
2. Adoptive cell therapy
3. Cancer vaccines
4. Cytokines
5. Oncolytic virus therapy

Question 15

what are check point inhibitors?

Answer 15

Check points are receptors on the surface of T cell. They suppress the T cell immune response to prevent T cells from attacking normal cells.

Types:

1. PDL1 receptor inhibitors
2. PD1 receptor inhibitors
3. CTLA-4 receptor inhibitors

Question 16

what is adoptive cell therapy?

Answer 16

• T cells are isolated from the patients. Modification and multiplication of those cells in the laboratory and then re-injection back to the patient circulation
• CAR-T – chimeric antigen receptor T-cell – therapy
• Very expensive! One session = £280000
• Licensed in the UK for B cell CLL and lymphoma (DLBCL)

Question 17

what are cancer vaccines?

Answer 17

• Sipuleucel-T is the first human cancer treatment vaccine to receive FDA approval. The treatment is personalised , using a patient’s own dendritic to create an immunostimulatory vaccine.
• Licensed for metastatic prostate cancer.

Question 18

what are cytokines?

Answer 18

• They are small proteins naturally produced and secreted by several immune system cells. They are crucial in signaling between immune cells, as well as between immune cells and several other cell types in the body
• Interleukin 2 (IL-2) is the only cytokine licenced to treat cancer (Kidney and melanoma)

Question 19

what is oncolytic virus therapy?

Answer 19

• Viruses target particular cancer. The virus will infect the cancer cell and replicate itself. This results in destruction of the cancer cell, releasing the tumour antigens and activating antibodies. T-cells will be activated and generates antitumor response causing the cancer cell to die
• T-VEC is an intra-lesionally delivered vaccine, contains a genetically engineered herpes simplex virus type 1 (HSV-1) that selectively replicates in tumour, lyses tumour cells, while promoting antitumor immunity. It is licenced in melanoma.

Question 20

what are the side effects of immunotherapy?

Answer 20