Personalised Medicine – Case Study Herceptin® Trastuzumab (Herceptin®) is a drug which is prescribed for some types of breast cancer. Some cancers have too much of a protein called human epidermal growth factor receptor 2 (HER2) on the surface of their cells. These are called HER2 positive cancers. The extra HER2 receptors stimulate the cancer cells to divide and grow. Herceptin locks on to the HER2 protein. This blocks the receptor and stops the cells from dividing and growing. Herceptin® only works in people who have cancer with high levels of the HER2 protein. Several tests are available to measure HER2 levels. Testing can be done at the same time as initial cancer surgery, or samples of cancer cells from previous biopsies or surgery may be used. Patients who test positive for this HER2 mutation are likely to respond well to Trastuzumab. The drug can shrink tumours, slow disease progression and increase survival. Unlike most chemotherapy drugs Trastuzumab kills just cancer cells leaving healthy cells intact. http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Biologicaltherapies/Monoclonalantibodies/Trastuzumab.aspx http://www.gene.com/

Personalised Medicine – Case Study Herceptin® QUESTIONS: 1. What condition does the drug Hercepton® treat? 2. In what way can Hercepton® be described as ‘personalised medicine’? 3. HER2 positive cancers have too much HER2 on the surface of their cells. What does this excess HER2 do? 4. What effect does Hercepton® have on the HER2 protein? 5. How can you measure HER2 levels? 6. In what way is Hercepton® unlike most chemotherapy drugs. Look up one of the web-links below and describe some of the reactions of patients to Hercepton® treatment. http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Biologicaltherapies/Monoclonalantibodies/Trastuzumab.aspx http://www.gene.com/

Personalised Medicine – Case Study Abacavir Genetic testing has dramatically reduced the number of people suffering side-effects to HIV medicines. Abacavir is an effective anti-retroviral treatment for HIV (the virus that causes AIDS). Unfortunately around 5% of patients suffer a severe side-effect to his drug, such as rash, fatigue and diarrhoea. The patients are suffering a 'hypersensitivity' reaction. This means that their immune systems is overreacting to the drug. Scientists and doctors thought that the genes controlling the way that people's immune systems respond might be responsible for the side-effects. This turned out to be the case. In 2002, two groups identified a particular gene variant (HLA-B*5701) as the key susceptibility factor. Clinical trials showed that screening patients for HLA-B*5701 before treatment dramatically reduced the number of hypersensitivity reactions. Use of the test is also cost-effective. Screening patients with HIV for HLA-B*5701 is now a routine part of clinical practice in the UK and included in HIV treatment guidelines. http://aidsinfo.nih.gov/drugs/257/abacavir/0/patient http://www.medcohealth.com/medco/corporate/home.jsp?articleID=CorpPM_Abacavir

Personalised Medicine – Case Study Abacavir QUESTIONS: What does ‘anti-retroviral’ mean? What is meant by a hypersensitivity reaction? What effect did screening patients for HLA-B*5701 have? Using this website describe some of the side-effects of Abacavir: http://aidsinfo.nih.gov/drugs/257/abacavir/0/patient 5. Look up the Use and Test Details for Abacavir and explain how the tests are carried out. http://www.medcohealth.com/medco/corporate/home.jsp?articleID=CorpPM_Abacavir

Personalised Medicine – Case Study Glivec® Another good example of personalised medicine for cancer treatment is Glivec®. This therapy is specifically used to treat forms of chronic myeloid leukaemia (CML) and a form of acute leukaemia. These conditions are caused by an abnormal chromosomal rearrangement. This rearrangement creates a mutant growth-promoting protein in white blood cells that causes them to become cancerous. The drug recognises this mutant protein which is present in these forms of leukaemia. What happens is a gene gets moved from one chromosome to another when a cell is dividing. This causes two genes that are normally completely separate to join together (fuse). This new, abnormal ‘fusion’ gene stops the bone marrow stem cells from maturing into normal blood cells. These abnormal cells are the leukaemia cells . When doctors look at the leukaemia cells they can often see a chromosome that looks different. This new chromosome, caused by the fusion of the two genes, is called the Philadelphia chromosome. The Philadelphia chromosome is made when a gene on chromosome 9 is mistakenly transferred to chromosome 22. Doctors only give Glivec® to patients who have the Philadelphia chromosome as it is with those patients where the treatment will be effective. http://www.macmillan.org.uk/Cancerinformation/Cancertreatment /Treatmenttypes/Biologicaltherapies/Cancergrowthinhibitors/Imatinib.aspx

Personalised Medicine – Case Study Glivec® QUESTIONS: What does CML stand for? What does the chromosome rearrangement create? What does Glivic® recognise? Describe what happen to the chromosomes when the leukaemia develops What is the Philadelphia chromosome? What is a fusion gene? Why is important to test for the presence of the Philadelphia chromosome before giving Glivic® ?