Theme Leads: Professor John F. Marshall, Professor Tyson V. Sharp
Key Cancer Types: breast, lung, pancreatic
Understanding the basic biology of cancer – how it arises, eludes normal controls and orchestrates normal cells to collude in its ability to spread – is the bedrock of our cancer research because here lies the means to beat cancer. Our basic biology research has led to novel discoveries and has paved the way to potential new therapeutics.
Our recent discovery and development of a novel radiotracer for the cancer-associated integrin, avb6, has led to clinical trials in fibrosis and cancer. In addition, the discovery of the essential need for extracellular arginine by multiple cancer types has developed into several successful clinical trials.
In fact, our excellent success in targeting the metabolism will be enhanced once we appoint a new Professor of Cancer Metabolism in the coming year.
Additionally, current studies of LIMD-1 have identified sensitive signalling pathways in cancers deficient in this protein and we are currently validating the first targeted therapy for LIMD-1-negative lung cancers, which make up approximately 47% of lung adenocarcinomas and therefore may represent a significant new therapeutic option for a large number of patients with lung cancer. Current preclinical work is underway with the hope that this new drug will be in Phase II clinical trials soon.
We have also identified synthetic lethal interactions with loss of DNA mismatch repair genes in a range of tumour types and also loss of the metabolic enzyme ASS1 in mesothelioma. These synthetic lethal interactions represent novel means of therapeutically targeting specific subsets of a number of hard-to-treat cancers.
Furthermore, we have uncovered a novel adaptation mechanism that permits centrosome amplification in epithelial cancers: Loss of E-cadherin allows survival of cells with extra centrosomes. These findings will be used to develop biomarkers to identify patients that are sensitive to therapies that target cancer cells with extra centrosomes.
Image credit: Human oral squamous cell carcinoma cell, SEM. Anne Weston, LRI, CRUK and John Marshall, Tumour Biology Lab. CC BY-NC