Research » Renal Cancer
Approximately 275,000 cases of renal cancer (Globocan) are diagnosed annually worldwide with >115,000 deaths. In the UK, it is the 8th most common cancer with ~9,000 new cases annually and incidence is increasing. This is due in part to the increased detection of asymptomatic tumours.
Approximately 90% of renal tumours arise in the renal parenchyma and are called renal cell carcinomas (RCC). The most common histological subtype (~75%) is conventional (clear cell) RCC (ccRCC), which is associated with loss of the VHL tumour suppressor gene through a combination of mutation, methylation and loss of heterozygosity although other genes have also now been implicated including PBRM1, BAP1 and SETD2. Other subtypes include papillary and chromophobe.
About two-thirds of patients present with localised disease where surgery is largely curative, but a third will relapse after surgery. Detection of relapse or monitoring of response is reliant on imaging. For patients presenting with metastatic disease, 5-year survival is <10%. Inherently resistant to chemotherapy and radiotherapy, tyrosine kinase inhibitors such as sunitinib and pazopanib, that inhibit angiogenic pathways downstream of VHL, are the main therapies. Although overall response rates and survival are improved, individual responses remain variable and unpredictable with 10%- 30% of patients responding, ~40% achieving disease stabilisation, and ~20% displaying intrinsic resistance. The mammalian target of rapamycin (mTOR) inhibitor, everolimus is one of the second- line treatments.
There are no tissue or fluid biomarkers in routine use in patients with renal cancer and biomarkers with major benefits would allow:
- earlier diagnosis
- provide prognostic information (particularly for small renal masses)
- earlier detection of relapse
- prediction of response to therapies
We are addressing these issues with a series of proteomic projects using clinical fluids such as serum/plasma or urine and also tissues (FFPE and frozen)
An NIHR Biomarker Programme is also integrated with this research with one workstream involving collecting fluid and tissue samples from 800 RCC patients at diagnosis (and longitudinally for 200) at 12 centres in the UK together with clinical data and follow-up. These are being used to validate biomarkers, particularly those of prognostic or monitoring utility.
We are also involved in the EU-funded FP7 CAGEKID Programme, leading one of the workstreams involved in coordinating pathological review of samples. Part of the International Cancer Genome Consortium, this Programme involves 14 partners from 6 EU countries, Russia, and IARC and is aiming to identify biomarkers and understand the biology of RCC through whole genome resequencing, transcriptomic and methylation analysis of 100 tumours, with initial validation in a further 400 cases and further validation in an additional 2,000 cases.