Molecular markers to PREDICT drug response in kidney cancer patients

The aim of the PREDICT Consortium (Personalised RNA Interference to Enhance the Delivery of Individualised Chemotherapeutics and Targeted Therapies) is to identify molecular markers to help select patients that may benefit from drugs used to treat kidney cancer.

PREDICT is a European Consortium that was established by James Larkin and Charles Swanton in collaboration with a number of clinicians and scientists, including Stephane Oudard and Bernard Escudier in Paris, Andrew Futreal in Cambridge and Martin Gore in London. James Larkin is a Medical Oncologist at the Royal Marsden Hospital (RMH) specialising in the treatment of kidney cancer; Charles Swanton is also a Medical Oncologist at RMH and leads a laboratory that works on RNA interference, a powerful new molecular technique that has been used to identify markers that may help select treatments for patients with breast cancer.

This technique has never before been used to analyse kidney cancers. Molecular markers that predict the effect of particular therapies exist in several types of cancer e.g. 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 kidney cancer.   The development of molecular markers is important for a number of reasons; 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 in kidney cancer, the duration of benefit from drugs such as sunitinib (Sutent) 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 side effects 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 kidney 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.

The PREDICT Consortium are running clinical trials at a few hospitals in London. These clinical trials are suitable for patients that have recently been diagnosed with kidney cancer that has spread to other organs (metastatic kidney cancer) and are having surgery to remove the kidney.   A biopsy of the kidney cancer is taken, treatment with a drug (such as everolimus or sunitinib) is given for 6 to 8 weeks and then the planned surgery is undertaken. Sunitinib or everolimus are continued after surgery in the same way as normal to treat the metastatic kidney cancer.   This type of trial is now quite common in kidney cancer, but for the first time PREDICT will be using RNA interference techniques in Charles Swanton’s laboratory to analyse tumour samples from the trials in order to identify molecular markers that predict tumour shrinkage on everolimus or sunitinib.

James Larkin March 2010