Week 18 p2 Flashcards
Why do we need targeted therapy
• Standard treatment does not work
• Some cancer respond better to these treatments
• Side effects are bad
Given systemically i.e their action is limited
What is the aim of targeted therapy
Decrease the activity of onco-proteins
Give examples of cancer therapies
- Antibody based therapies
- Small molecules
- Immune checkpoint blockades- AB that block pathways to prevent the immune from attacking cancer cells
- Gene therapy based approached - use viral vectors to deliver corrected and functioning mutated gene
What is Kaplan Meier graph
Shows the probability of an event e.g. survival rate
What is antibody therapies
- Antibody bind to spefic proteins that can reduce their activity
- Bind to extracellular area
- AB are serum protein produced by B lymphocytes in response to antigen
- Hypervariable region detects antigens known as epitopes
- AB are from clonal expansion of a single antibody producing cell called monoclonal antibodies (mb)
Hint drugs that end in mab
How does antibody therapies work
• AB can act as anti oncogenic agents by blocking spefic growth factor receptors Eg Herceptin (Trastuzumab)
How does Herceptin (Trastuzumab) work
- Has high affinity for the extracellular domain of HER2
- Promotes an increased HER2 internalisation and degradation
Induces antibody dependent cytotoxic response
Evidence of Herceptin on survival
• Improves survival rate and disease free survival in women with HER+ BC
In this trial Herceptin was given to women after surgery and chemotherapy with or with RT
What is Cetuximab/Panitumumab
- Anti EGFR
- Used treat metastic colorectal cancer, lung cancer and head and neck cancer
- AB binds to and inhibits extracellular domain of EGFR
Given in combination with standard therapy
What are the side effects and resistance of antibody therapies
- SE: Herceptin= serve cardiac problems +milder effects
- R; Herceptin= HER2-,PI3K pathway mutation
- SE: Cetuximab= serve aches+ rash +milder effects too
R: Cetuximab=KRAS and BRAF mutation
How does immunotherapy and AB therapies work
- Trials for HE2 and EGFR antibodies
- HER2 and PD1/L1 inhibiting ab
- Causes secondary effects for resistances
- Such as Herceptin may cause mutation in HE2,prevent Mab binding and causes over expression of EGFR
Cetuximab will cause EFGR or RAS mutation so HER2 can compensate
What is small molecule treatment
- Chemical compounds that directly interfere with overactive signalling pathways in cancer cells
- Small chemical molecular can penetrate inside the cell
Hint ends with ib
What is Imatinib (gleevec) small molecule based treatment
For BCR-ABL and has high kinase activity]causing an increase in growth signalling and reduction in apoptosis
This drug binds to ATP binding pocky and stabilises the inactive form of BCR-ABL
What is the resistances for Imatinib (Gleevec)
- Resistance to treatment after an initial response and developed in 3 ways
- 1.muatation of BCR-ABL to inhibit binding BCR-ABL
- 2.overexpression by other mechanism
- 3.reistances cells can gain an selective advantage and patients relapse
How would this be solved
- Giving inhibitors such as bosutinib,nilotinin or ponatinib
- Increase dosage
- Last resort- bone marrow transplant
