Harnessing tumour diversity to improve survival outcomes in lung cancer

Prof Charles Swanton, University College London

A common problem with treating lung cancer is it can spread quickly and become resistant to cancer drugs. It is therefore very important to understand more about the disease, to develop new treatments and improve survival. For a long time it was assumed that a tumour consists of cells that are very similar to each other. Work by Professor Charles Swanton and his team has suggested that cells within a lung cancer tumour are variable and subject to evolution, where they change over time. This study uses new a new approach to study lung cancer, by looking at the origin and changes of the tumour, with the aim of identifying new anti-cancer approaches. It is part of the large TRACERx study, where samples are collected from different areas of the tumour, at different times.  These samples are then genetically sequenced, to see how they evolve.

Identification of genes that increase the risk of childhood cancers

Prof Nazneen Rahman, Institute of Cancer Research

Most childhood cancers are due to faulty genes that run through families, leading to more than one child being affected, or to a child having multiple cancers.

In 2006 Prof Rahman helped set up the international FACT (Factors Associated with Childhood Tumours) study, the largest of its kind in the world. This study now includes over 9000 individuals affected by childhood cancer and their family members. Collecting this information has allowed Prof Rahman to identify changes to the genetic code (mutations) in two genes, CTR9 and REST that cause the childhood kidney cancer, Wilms tumour.  These findings are very exciting, and this is the first time that any genes have been linked with this disease.

Speaking about the importance of this work, Professor Rahman said “Our findings are of immediate value to families, who now have an explanation for why their child got cancer. Moreover, we can now do a simple blood test to see which children in the family are at risk of cancer and may benefit from cancer screening, and which have not inherited the mutation and so are not at increased risk of cancer. This kind of information is really valuable for the families of children with cancer.”

The use of vaccinia virus in melanoma treatments

Professor Kevin Harrington, Institute of Cancer Research

Malignant melanoma is an aggressive form of skin cancer which has a poor prognosis. New treatments are required to combat the disease and improve survival. Using a virus, it’s possible to launch a double attack on cancer cells. By genetically modifying the virus, it can infect cancer cells specifically, but not healthy tissue. Once inside the cancer cell, the virus replicates rapidly, causing the cell to burst open. This spills virus into the area surrounding the tumour, activating the second phase of attack, where the immune system targets and destroys the cancer cells. Here, Professor Harrington’s team aim to develop the next generation of virus based therapies, which are based on the cold sore virus – Herpes Simplex. They hope to improve on their current treatment by altering the virus further, to insert genes which will stimulate the immune system to activate a response to the cancer cells, without having to wait for the virus to replicate enough. They will test a number of genes to find out which has the greatest effect, and test this alone and in combination with new immunotherapies that are already being used in the clinic.

Exhalation kinetics of volatile aldehyde biomarkers in oesophago-gastric adenocarcinoma

Professor George Hanna, Imperial College London

Oesophageal and gastric cancer are some of the most common in the world, and with a lack of disease-specific symptoms, are often detected in the late stages.  As a result, gastric cancer is the third leading cause of global cancer-related death, with only 1/3 of patients having potential for curative treatment, and a 5-year survival rate of just 13%.  A key strategy for improving survival is early detection. The aim of Professor George Hanna and his team is to refine a breath test that would work in the same way as an alcohol breathalyser test, and could detect gastric cancers in the early stages. The researchers have already made significant progress in the development of a breath test, which is already being tested in clinical trials. In this project they plan to refine the model through better identification and quantification of the molecules found in exhaled breath. This would bring the research much closer to use in the clinic, and ensure confidence in test results.

Personalised Breast Cancer Medicine Initiative

Professor Calos Caldas & Dr Jean Abraham, University of Cambridge

All cancer is caused by mutations in genes in the body’s cells. It is now known that within a simple type of cancer many different gene mutations can occur which will affect prognosis and treatment outcomes. This project will study the full genome in each patient at Addenbrooke’s Hospital, Cambridge for 5 years to identify mutations and monitor response to different drugs according to patients’ individual genetic make-up. This will be a first step in personalised drug treatment targeting gene mutations.

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