Cancer Therapeutics Flashcards
What is the most treatable type of cancer?
Non-malignant melanoma
Why do survival rates differ between Local, Regional and Distant tumours?
Local tumours show no sign of spreading and thus if excised will result in halting of tumour progression, high survival chance.
Regional tumours that start spreading to neighbouring tissues can have good survival rates if treated after diagnosis.
Distant tumours that have spread to different sites are difficult to treat as they are spread throughout the body.
What current treatments are there for breast cancer?
Masectomy - removal of breast tissue
Chemotherapy
What is the estimated level of over-diagnosis for breast cancer?
For every 56 cases, 5 diagnosed breast cancer and saved lives, 2 overdiagnosed.
It is thought that 5-10 women undergo unnecessary surgery for each women whose life was saved by surgery.
What are the chances of a women dying from breast cancer she never undergoes screening?
1/200 chance that is a fatal decision
What are the chances a women who is diagnosed with breast cancer will undergo unnecessary surgery?
1/65 chance of unnecessary surgery
What factors affect the effectiveness of screening and successful treatment?
Efficacy of the screening method
Potential of effective treatment
Efficacy and accuracy of the screening method must outweigh the associated costs of the screening and the associated risks of the treatment = Balance
What is the purpose of a Pap smear?
Pap smears attempt to detect cervical cancer (introduced in the 1930s)
Why have survival rates of cervical cancer improved significantly over the last 40 years?
Screening improvements
What is the current screening technique used to diagnose bowel cancer?
FOBT Foecal Occult Blood Test
Blood in the foeces can be triggered by the formation of polyps on the colon lining.
What techniques are avaiable to diagnose bowel cancer?
FOBT Foecal Occult Blood Test
Colonoscopy
Is FOBT or Colonoscopy more specific for the detection of polyps and colon cancer?
Colonoscopy detects 4-5x more polyps and cancers than FOBT
What is the difference in cost between FOBT and Colonoscopy?
Colonoscopy is 10x more expensive than FOBT but Colonoscopy is 10x better at polyp detection.
What is a future technique for the detection of polpys and colon cancer?
Virtual colonoscopy
Computerised tomography (CAT scan). A series of X-rays. Almost as sensitive as colonoscopy but 1/3 cost and lower risk.
What are the advantages of chemotherapy?
Very toxic to target cells
Knowledge of the tumour is not required
Radiation can be targeted
What are the disadvantages of conventional cancer therapies?
Surgery can be difficult and damaging
Toxicity from chemotherapy is not specific to cancer cells
Mechanism of chemotherapy involves DNA damage, cells that survive therapy can have sustained more damage than the starting cells.
What types of targeted therapies for cancer are there?
Antibodies (most end in mab)
Small molecule inhibitors (end in nib) (kinase inhibitors, block phosphorylatory activity and prevent oncogene activity)
Synthetic Lethality (targets weakness of cancer cell, for example if one DNA pathway is already damaged, the second will be targeted, killing the cells)
Angiogenesis Inhibitors (starves cancer, can block VEGF)
What makes a good target for a cancer therapy?
Tumour suppressors are poor targets as gene function must be restored
Oncogenes are much better targets as have activating mutations. These are actively promoting growth.
What is a Phase 1 stage for in drug development?
To check safety and appropriate dosage.
What are the possible recommendations from NICE regarding a drug being introduced into the NHS?
Recommended
Optimised - recommended but with restrictions (perhaps only a subset of patients)
Only in research (promising approach, but requires further evidence) (used only as part of a well-designed clinical trial)
Not recommended (lacks evidence to support clinical effectiveness) (substantially less cost effective than is normally considered to be an acceptable use of NHS resources)
What are quality-adjusted life years (QALY)?
QALY is a measure of disease burden, including both the quality and duration of life lived.
What is an ICER?
ICER = Incremental cost-effectiveness ratio
NICE accepts as cost-effective, interventions with an ICER of <£30,000 per QALY
What is vemurafenib?
Vemurafenib is a BRAF inhibitor
- £1750/week
- Used to treat locally advanced metastatic BRAF V600 mutation positive malignant melanoma
- 3x cost of existing chemo treatment
What is NICE?
NICE = National Institute for Clinical Excellence
Decide which drugs the NHS will use
What increase in life expectancy do most new drugs provide?
3 months
What is ONYX-015?
ONYX is a therapeutic, a virus that lacks the EIB gene.
EIB normally binds to p53 and causes its degradation.
The virus cannot replicate in cells with the wildtype p53.
If the virus infects a cell with inactive p53, it replicates causing cell destruction that releases the virus.
What drugs can turn p53 back on?
Gendicine (China) and Advexin (USA)
Essentially carries p53 into cells.
What types of cancers are Advexin/Gendicine used to treat?
Head and Neck cancers
p53 mutations are common in 45-70% of tumours
Usually treated with surgery and/or radiotherapy. But the tumours often recur. High level of morbidity and chemotherapy is not effective.
Tumours with p53 mutations can be targeted with ONYX-015 or Advexin/Gendicine.
The virus is injected directly into the tumour and has some response.
How can mouse antibodies be humanised?
The functional parts that will recognise the animal antigen are fused genetically to the coding sequence from the human antibody.
How do antibody drugs kill tumours?
- Can bind to receptor and block the function
- Can be linked to a drug (toxin)
- Can affect protein function directly
- Recruit other immune cells (T cells, killer cells)
- Hyping up Immune system to recognise the cancer cell
What is CTLA4?
Protein found on the surface of T cells which subdues the activity of the cells.
It is associated with adverse inflammatroy responses in skin and GI tract.
What is PD1?
PD1 is a receptor on the surface of a T cell that binds to a ligand PDL1 on the surface of the tumour.
The cancer cell is switching the T cell off. A common mechanism employed by cancer cells.
What is Nivolumab?
Nivolumab is a PD-1/PD-L1 checkpoint inhibitor
It offers a 3 month life extension for late stage metastaic NSCLC.
What is the role of Preimplantation Genetic Diagnosis (PGD) in cancer therapy?
PGD is a preventative measure.
A cell embryo is taken cells removed from the zona pellucida for analysis. It is then screened for cancer causing mutations.
How can targeting VEGF be a cancer therapy?
VEGF can be blocked which prevents blood vessel growth to starve cancer cells. It is often used in addition to other treatments as it not currently effectient enough to be used alone.
How can dendritic cell therapy be used to treat cancer?
The first therapeutic vaccine (Provenge) uses leukapheresis to isolate dendritic cells and macrophages (APCs) that can present antigens to other immune cells.
APCs cultured with prostatic acid phosphatase (PAP). This vaccine is infused into the patient with the aim of starting up poweful immune cells. This tries to neutralise the tumour cells that express PAP.
