Research to identify molecular markers to help select patients that may benefit from treatment with a particular drug is in the early stages. Researchers are trying to identify gene mutations that will enable them to predict the response to a particular drug in renal cancer patients. This approach is based on the principle that genetic mutations cause cancer; however, these mutations can be different, even for the same cancer type. As a result of these genetic mutations, one person might have a renal cancer that responds to treatment with a biological therapy, while another patient will not.
Molecular markers that predict the effect of particular systemic treatments exist in several types of cancer, for example; HER2 for trastuzumab (Herceptin®) in breast cancer; c-KIT for imatinib (Glivec®) in gastrointestinal stromal tumours; EGFR for erlotinib (Tarceva®) in non-small cell lung cancer; and KRAS for cetuximab (Erbitux®) in colorectal cancer. All of these molecular markers are in routine clinical use but there are currently no such markers in renal cancer.
The development of molecular markers is important because only patients who are likely to benefit from the therapy will be treated, thereby potentially increasing average benefits from treatment across large groups of patients. For example, in clinical trials for renal cancer, the duration of benefit from drugs such as sunitinib is currently about 11 months. About a third of patients will derive very little benefit from treatment; knowing who these patients are in advance would spare them from both ineffective treatment and the side effects of sunitinib and, as a consequence, increase the average benefit of sunitinib treatment in the patients being treated with the drug. Patients destined not to benefit from sunitinib could be treated with other drugs or in clinical trials with significant further potential benefits.
The use of molecular markers also means that high cost drugs might be approved more readily in specific situations or in rare types of cancer. Therefore, the development of molecular markers to guide treatment in renal cancer may increase our understanding of the disease as well as having a number of benefits for both patients and societies struggling to fund high cost treatments for cancer.
Three European research groups are investigating molecular markers for renal cancer;
PREDICT (Personalised RNA interference to Enhance the Delivery of Individualised Chemotherapeutics and Targeted therapies) is a European consortium led by researchers from the Royal Marsden Hospital in London. They are using a powerful new molecular technique to identify markers that may help select treatment for renal cancer patients. This technique has already had some success with identifying molecular markers for breast cancer. The PREDICT Consortium are running clinical trials with advanced renal cancer patients at a few hospitals in London [1].
CAGEKID (Cancer GEnomics of the Kidney) is led by researchers from France and again is a Europe-wide research consortium. The research will provide the first systematic analysis of the renal cancer site providing new insights into the disease origins with application for diagnosis and treatment. It addresses a major need to identify new biological markers for RCC [2].
EuroTARGET is a collaborative European study on “Targeted therapy in Renal cell cancer: GEnentic and Tumour related biomarkers for response and toxicity”. The project is investigating the DNA of RCC patients from blood and tissue samples with the aim of discovering a biomarker to predict the response to anti-angiogenic drugs. There are 15 collaborators from across Europe, including the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust [3].