L20: Principles of Cancer therapy Flashcards
What is the difference between Chemotherapy and Drug therapy.
Chemotherapy: the use of chemicals to kill disease causing cells in the body - eg. bacteria, fungi, viruses, cancer
vs Drug therapy: using chemicals to modulate body processes - eg. antihypertensive
What is selective toxicity and how is it achieved in chemotherapy
Selective toxicity is the goal of chemotherapy: It is to produce toxic effects in the cancer cell without/less effects in the host cells.
This is achieved by exploiting differences between normal host cells and disease cells- eg
- there is a unique target in the pathogen,
- the target is structurally different in the pathogen
- the target is functionally different in the host -eg. more cells undergoing end phase of mitosis in cancer cells than normal cells
Describe first order kinetics of tumour cell growth/ Chemotherapy
Tumour growth: Divides with constant doubling time. Clinically evident at 10^8. Lethal 10^12.
Chemo: Each dose kills a constant proportion of tumour cells so repeated doses are required to completely erradicate tumour cells past the clinically evident tumour
What is the Mechanism and example of Alkylating agents and Platinum based drugs
M: Binds to DNA forming crosslinks to damage it.
Alkylating eg. cyclophosphamide: crosslinks guanine
Platinum eg. Cisplatin: cross links purine bases
What is the Mechanism and example of Antimetabolites
M:Inhibiting DNA synthesis in the S phase of mitosis
eg. methotrexate : dihydrofolate reductase inhibitor (folate inhibitor)
What is the Mechanism and example of Topoisomerase interactive drugs
M: Inhibit enzymes in the nucleus that control how DNA is organised so DNA can’t function properly - during replication
eg. Doxorubicin
What is the Mechanism and example of Antimicrotubule drugs
M: Bind microtubule proteins involved in mitotic spindle preventing proper mitosis in M phase
eg. Paclitaxel
What is the Mechanism and example of Hormonal agent
M:Block production or action of sex steroids at the receptor which prostate cancer, breast cancers depend on for progression of growth.
Eg, Tamoxifen is oestrogen receptor antagonist
What is the Mechanism and example of Targeted therapies
M:Block oncogenic proteins
Eg. Imatinib which inhibits
1. BCR-ALK- constitutive abnormal tyrosine kinase.
- KIT tyrosine kinases - for platelet derived growth factor and stem cell factor cell events
Both leads to inducing apoptosis and inhibit proliferation in tumour cells.
What is the mechanism and example of Vascular targeting therapies
M:Inhibit angiogenesis
eg. bevacizumab
Binds to vascular endothelial growth factor.
What are the major adverse effects of cancer chemotherapy based on mechanism of action, and where exactly
- Antiproliferative effect: organ systems with high rates of proliferation
eg. myelosuppression in the bone marrow, mucositis- ulceration/inflammation of mucus linings of the mouth, alopecia, sterility in the gonads - Mutagenesis (damage DNA)
eg. causing second cancer, and damaging to developing fetus teratogenicity by inducing mutations. - Microtubule disturbance - peripheral neurotoxicity
- Sex steroid deficiency: decreased libido, impotence, flushing/menopausal symptoms
What are the indications for cancer chemotherapy
- To cure (primary treatment for cancers in younger people: acute lymphoblastic leukaemia, testicular cancer, lymph gland cancer
- With surgery : given to eradicate micro metastatic disease to stop recurrent cancers
- With radiotherapy: combined modality treatment- to enhance the radiotherapy for neck and head and cervical cancer.
- Palliation: Improve symptoms and survival time, quality of life in lung cancer
What is Therapeutic index and how calculated
Therapeutic index (TI): indicator of selective toxicity; ratio of dose (conc for 50% effect-ED50) for toxic effect/ dose for therapeutic activity
This is generally the range of concentrations between the two curves (tumour cells and normal cells) point of 50% killing concentration.
