Molecular investigation of pathology archives V1 10-05-19
Research type
Research Study
Full title
Use of pathology archive material to understand the molecular basis for cancer development and progression, drug resistance and drug toxicity in solid tumours.
IRAS ID
238785
Contact name
Tyson Valentine Sharp
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
10 years, 6 months, 1 days
Research summary
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. The 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern.
Recent successes in targeting the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis of immune checkpoint inhibition represent a major immunotherapeutic advance in treating lung cancer. Furthermore, it is believed that such immunotherapies in combination with targeted chemotherapies hold great promise to significantly improve outcome for lung cancer patient.
LIMD1 is a lung tumour suppressor gene that is lost early, and with very high frequency, in the development of lung cancer. Furthermore, we have very exciting novel data that reveal the loss of LIMD1 results in increased expression of PD-L1.
We hypothesise that LIMD1 controls PD-L1 expression levels and that loss of LIMD1 promotes tumour immune evasion.
We plan to Validate PD-L1 and LIMD1 expression in lung human lung cancer and other solid tumours. In this section of work, we will perform protein expression analysis on ~200-300 tumour resected tissues samples via IHC. This latter analysis will be in close collaboration with Prof Michael Sheaff and his team of histopathologists at Barts and the London SMD. This analysis will explore correlation between PD-L1 and LIMD1 expression, and stratify patients based on their PD-L1 and LIMD1 status. This will be further correlated with response to anti-PD-1/PD-L1 blockade therapy and other clinicopathological data.
Expected outcomes: Here we will reveal for the first time the degree of correlation between LIMD1 loss in lung cancer and deregulation of PD-L1. In addition to this we will be able to examine the clinicopathological associations and correlations that may provide new insight into patent stratification for form increased efficacy of immune blockage therapies.REC name
London - London Bridge Research Ethics Committee
REC reference
19/LO/0975
Date of REC Opinion
19 Jun 2019
REC opinion
Favourable Opinion