Lecture 20: Principles of cancer therapy Flashcards
What is chemotherapy?
- Using chemicals to kill disease causing cells in the body i.e bacteria, fungi, viruses and cancer
What is drug therapy in contrast to chemotherapy?
- Using chemicals to modulate body processes
i. e BP, mood
Describe selective toxicity:
- Selective toxicity is the goal of cancer chemotherapy
- Occurs when toxicity is produced in the cancer cell without (or with less) effects in the host cells (of drug therapy)
- Achieved by exploiting differences between host cells and diseased producing cells.
What are some disease cell characteristics exploited in selective toxicity?
- There is a unique target in the pathogen
- The target is structurally different in the pathogen
- The target is functionally different in the host
What is therapeutic index?
- Important indicator of selective toxicity
- Ratio of dose required to produce a toxic effect divided by the dose required to produce desired effect
Classification of cancer chemotherapy drugs; according to mode of action. What are the 8 categories?
- Alkylating agents
- Platinum based drugs
- Antimetabolites
- Topoisomerase interactive drugs
- Anti-microtubule drugs
- Hormonal agents
- Target therapies
- Vascular targeting therapies
Whats the action of cyclophosphamide
Alkylating agents
- Binds DNA
- i.e Cyclophosphamide
Whats the action of cisplatin
Platinum based drugs
- Binds DNA
- i.e Cisplatin
Whats the action of methotrexate
Antimetabolites
- Inhibit DNA synthesis
- i.e Methotrexate
Whats the action of doxorubicin
Topoisomerase-interactive drugs
- Inhibit topoisomerases
- i.e doxorubicin
Whats the action of paxilatcel
Antimicrotubule drugs
- Bind microtubules
- i.e paxlitacel
Whats the action of Tamoxifen?
Hormonal agents
- Blocks production or action of sex steroids
- i.e Tamoxifen
Whats the action of imatinib?
Target therapies
- Block oncogenic proteins
- i.e imatinib
Whats the action of bevacizumab?
Vascular targeting therapies
- Inhibit angiogenesis
- i.e bevacizumab
Whats the first order kinetics of tumour growth and whats the implication for chemo?
Cancer cells double at a constant rate
Chemo kills only a portion of cells , thus repeated doses required, continued once no longer clinically evident for this reason
What is the criteria for combination chemotherapy?
- More effective than using a single agent
Criteria:
- Some activity as a single agent
- Differing mechanisms of action
- Different side effect profiles
What is the BEP combination chemotherapy for testicular cancer?
Bicomycin
Etoposide
cisPlatin
- Bicomycin: Induces DNA breaks; toxic in lungs
- Eptoposide: Topoisomerase 2 poison, toxic to bone marrow
- Cisplatin: Induces DNA crosslinks, toxic to peripheral nerves
What are some adverse effects from chemo?
- > Antiproliferative ; Myelosuppresion, mucositis, alopecia, sterility
- > Mutagenesis: Secondary cancers, teratogenicity
- > Microtubule disturbance; Peripheral neurotoxicity
- > Sex steroid deficiency; Decrease labido, flushing
What are some indications for cancer chemotherapy:
- Curative (those cancers that respond well)
- With surgery (additive)
- With radiotherapy
- Palliation; prolong survival
