Anti cancer drugs

Question 1

What is the target of anti cancer drugs?

Answer 1

Highly proliferating cells which includes cancer cells but also cells that form hair, GIT lining and bone marrow.

Question 2

List the acute side effects of chemotherapy

Answer 2

1. Bone marrow depression (myelosuppression): pancytopenia, leukopenia, thrombocytopenia
2. GI toxicity: nausea and vomiting
3. Alopecia (hair loss)
4. Peripheral neuropathy

Question 3

List the chronic side effects of chemotherapy

Answer 3

Myelosuppression can result in opportunistic infections

1. Cardiotoxicity
2. Pulmonary toxicity
3. Nephrotoxicity
4. Neurotoxicity

Question 4

Differentiate between cell cycle SPECIFIC and NON SPECIFIC drugs

Answer 4

Cell cycle specific drugs - drugs that only kill during specific parts of the cell cycle, either S or M phase

Cell cycle non-specific drugs - drugs that kill throughout the cell cycle

Question 5

List the 4 classes of cell cycle non-specific drugs

Answer 5

1. Alkylating drugs
2. Platinating drugs
3. Cytotoxic antibodies
4. Topoisomerase inhibitors

Question 6

List the 2 classes of cell cycle specific drugs

Answer 6

1. Anti-metabolites
2. Mitotic inhibitors

Question 7

What is the MOA of alkylating drugs and name a alkylating drug

Is it cell cycle specific or non specific?

Answer 7

NON SPECIFIC

Alkylating drugs crosslinks inter-strands of DNA so it cannot unwind for replication and transcription (ie. join 2 strands of DNA together so they cannot unravel that easily)

Can also cause double and single strand DNA breaks.

Examples include: cyclophosphamide and chlorambucil

Question 8

What is the MOA of platinum drugs and name a platinum drug

Is it cell cycle specific or non specific?

Answer 8

NON SPECIFIC

Platinum-based drugs act similar to alkylating agents but cross link DNA more intra-strand than inter-strand.

Examples include: cisplatin, carboplatin and oxaliplatin
Anything that ends with a ‘-platin’ is a platinum drug.

Question 9

For which group of patients is platinum drugs contraindicated in and why?

Answer 9

Patients with renal pathologies and problems.

Platinum drugs are eliminated via excretion in urine and not metabolised in the liver.

Question 10

What is the MOA of anti metabolites and name an anti metabolite

Is it cell cycle specific or non specific?

Answer 10

SPECIFIC -> since it only impairs DNA replication specifically

Prevents DNA replication by inhibiting purine and pyrimidine synthesis.

Examples include methotrexate and 5-flurouracil

Question 11

What is the MOA of cytotoxic antibodies and name a cytotoxic antibody

Is it cell cycle specific or non specific?

Answer 11

NON SPECIFIC

Mechanisms include:
1. Intercalating (going in between) base pairs along DNA strands to prevent replication.
2. Creating free oxygen radicals that damage DNA
3. Inhibits topoisomerase 2

Examples include: **DOXORUBICIN and daunorubicin

Question 12

What is the most used cancer drug and what class of anti cancer drug does it belong to?

List its MOA.

Answer 12

Doxorubicin

Cytotoxic antibody

Mechanisms include:
1. Intercalating (going in between) base pairs along DNA strands to prevent replication.
2. Creating free oxygen radicals that damage DNA
3. Inhibits topoisomerase 2

Question 13

What is the MOA of mitotic inhibitors and name the 2 classes of mitotic inhibitors

Is it cell cycle specific or non specific?

Answer 13

SPECIFIC

Disrupts microtubule function (involved in mitosis, splitting of chromosomes)

Class 1: Vinca alkaloids (start with ‘Vin-‘)
MOA: Bind to polymerising end and prevent microtubule ELONGATION.
Eg: Vinblastine, vincristine

Class 2: Taxanes (end with ‘-taxel’)
MOA: Binds along the microtubule, stabilising it and preventing it from shortening
Eg. Paclitaxel, Docetaxel

Question 14

Differentiate between the MOA of vinblastine and paclitaxel

Answer 14

Vinblastine prevents microtubule elongation while paclitaxel prevents microtubule shortening by stabilising it.W

Question 15

What is the cardiovascular effect of taxanes?

Answer 15

Bradycardia

Question 16

What is the MOA of topoisomerase inhibitors and name a topoisomerase inhibitor

Is it cell cycle specific or non specific?

Answer 16

NON SPECIFIC

Inhibits topoisomerase 1 (unfolds DNA) and 2 (folds DNA back) for transcription and replication.

Disrupt transcription and replication = no mitosis = stunt cell growth

Eg: Irinotecan (Type I) and Etoposide (Type II)

Question 17

List the type 1 and 2 topoisomerase inhibitor drugs

Answer 17

1: Irinotecan
2. Etoposide

Question 18

What is imatinib, which type of cancer is it used for and what is its MOA?

Answer 18

Imatinib is a type of cancer growth blocker called a tyrosine kinase inhibitor (TKI).

Used to treat CML

MOA: competes with ATP for BCR-ABL, preventing signalling for growth

Question 19

Describe the MOA of avastin

Answer 19

Avastin binds vascular endothelial growth factor (VGEF) before it can bind with VEGF receptor, preventing angiogenesis.

Question 20

** Describe CAR T cell therapy, its structure and process

Answer 20

Chimeric antigen receptor (CAR) T cell therapy

Structure:
CARs are synthetic receptors composed of an extracellular antigen-binding domain, a transmembrane domain, and one or more intracellular signaling domains.
- Extracellular antigen -> recognise tumour antigens
- Intracellular antigen -> costimulatory signal for stronger activation

Newer gen of CAR have >1 costimulatory signal which the 1st gen did not have.

Process:
1. Extract T cell from patient
2. Insert the gene encoding for the CAR into the T cell (through virus)
3. Proliferate the T cells in vitro
4. Pre-condition patient by lowering white blood cell count so they accept the incoming T cells
5. Insert the modified T cells into patient

Question 21

How does CAR T cell exert its effect on tumor cells?

Answer 21

Binding of the CAR to the target antigen triggers the activation of the CAR T cell.

Intracellular signaling domains within the CAR initiate signaling cascades that lead to T cell activation, proliferation, and the release of cytotoxic molecules.

Activated CAR T cells specifically target and kill cancer cells expressing the target antigen through mechanisms such as the release of cytotoxic molecules (e.g., perforin and granzymes) and the induction of apoptosis (cell death).