Edward Law

2016 AFPGR Participant

 

Copy number alterations predict patient response to novel drugs in non-small cell lung cancer
About Edward
Edward recently submitted his PhD in Cancer Studies under the supervision of Professor Dean Fennell. Edward is interested in translational cancer research, which is moving discoveries from the lab into the clinic as quickly as possible. In particular, he focuses on exploiting the genetics of patient tumours to enhance their survival.

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Research Overview and Findings

Lung cancer remains a stubborn set of diseases to treat.  Over 35,000 people in the UK died of lung cancer in 2012. Only 5% of people diagnosed with the disease will live 10 or more years. Compared to a disease like testicular cancer, where 98% of people live 10 or more years, clearly there is a lot of work to do in lung cancer research. These tumours are genetically complex and must be dealt with using a "personalised medicine" approach: matching the tumour genetics to the best drugs available.

Copy number alterations (CNAs) are changes in the number of copies of particular genes in individual tumours. To date little work has been performed in linking tumour CNAs to patient outcome for targeted drugs. One exciting class of targeted agents are HSP90 inhibitors, which enter cancer cells and block HSP90 activity. This prevents the maturation of many proteins required by cancer cells to grow and survive. Recently, the “GALAXY-1” clinical trial of patients with a form of lung cancer call non-small cell lung cancer (NSCLC), investigated patient response to the HSP90 inhibitor ganetespib plus docetaxel, a standard chemotherapeutic agent. The outcome for some patients in this trial looked positive, but we decided to take some samples of patient tumours to see if analysis of their genetics, specifically copy number alterations, could improve patient survival.

We combined an array-based system and novel bioinformatics methodology to identify potential CNA “biomarkers” from tumour DNA, which predict patient response to ganetespib plus docetaxel for the GALAXY-1 trial. The results suggest several CNAs which are responsible for sensitivity to the drug combination, resulting in longer survival times. Furthermore, the more of these CNAs a patient has, the more likely they are to live longer when treated with ganetespib and docetaxel. Ultimately this resulted in a possible doubling of survival times for a subgroup of patients treated with the novel combination of drugs. This work is now being validated by repeating the analysis on patients from the phase-III trial, GALAXY-2.

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