Anti cancer drugs Flashcards
(21 cards)
What is the target of anti cancer drugs?
Highly proliferating cells which includes cancer cells but also cells that form hair, GIT lining and bone marrow.
List the acute side effects of chemotherapy
- Bone marrow depression (myelosuppression): pancytopenia, leukopenia, thrombocytopenia
- GI toxicity: nausea and vomiting
- Alopecia (hair loss)
- Peripheral neuropathy
List the chronic side effects of chemotherapy
Myelosuppression can result in opportunistic infections
- Cardiotoxicity
- Pulmonary toxicity
- Nephrotoxicity
- Neurotoxicity
Differentiate between cell cycle SPECIFIC and NON SPECIFIC drugs
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
List the 4 classes of cell cycle non-specific drugs
- Alkylating drugs
- Platinating drugs
- Cytotoxic antibodies
- Topoisomerase inhibitors
List the 2 classes of cell cycle specific drugs
- Anti-metabolites
- Mitotic inhibitors
What is the MOA of alkylating drugs and name a alkylating drug
Is it cell cycle specific or non specific?
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
What is the MOA of platinum drugs and name a platinum drug
Is it cell cycle specific or non specific?
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.
For which group of patients is platinum drugs contraindicated in and why?
Patients with renal pathologies and problems.
Platinum drugs are eliminated via excretion in urine and not metabolised in the liver.
What is the MOA of anti metabolites and name an anti metabolite
Is it cell cycle specific or non specific?
SPECIFIC -> since it only impairs DNA replication specifically
Prevents DNA replication by inhibiting purine and pyrimidine synthesis.
Examples include methotrexate and 5-flurouracil
What is the MOA of cytotoxic antibodies and name a cytotoxic antibody
Is it cell cycle specific or non specific?
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
What is the most used cancer drug and what class of anti cancer drug does it belong to?
List its MOA.
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
What is the MOA of mitotic inhibitors and name the 2 classes of mitotic inhibitors
Is it cell cycle specific or non specific?
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
Differentiate between the MOA of vinblastine and paclitaxel
Vinblastine prevents microtubule elongation while paclitaxel prevents microtubule shortening by stabilising it.W
What is the cardiovascular effect of taxanes?
Bradycardia
What is the MOA of topoisomerase inhibitors and name a topoisomerase inhibitor
Is it cell cycle specific or non specific?
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)
List the type 1 and 2 topoisomerase inhibitor drugs
1: Irinotecan
2. Etoposide
What is imatinib, which type of cancer is it used for and what is its MOA?
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
Describe the MOA of avastin
Avastin binds vascular endothelial growth factor (VGEF) before it can bind with VEGF receptor, preventing angiogenesis.
** Describe CAR T cell therapy, its structure and process
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
How does CAR T cell exert its effect on tumor cells?
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).
