New era of personalised medicine for bowel cancer
Bowel cancer affects 1/23 Australians in their lifetime, and half of these patients will succumb to their disease. Chemotherapeutic options for advanced disease have expanded in recent years, however no biomarkers have been available to inform choice of therapy – until now. Dr Vicki Whitehall and Prof Barbara Leggett of the Conjoint Gastroenterology Laboratory at QIMR have developed a molecular test for the K-ras oncogene, which will be used by oncologists to determine the optimal therapy for patients with advanced bowel cancer. Cetuximab (marketed in Australia by Merck Serono as ErbituxÒ) is a monoclonal antibody therapy which blocks growth factor binding to the epidermal growth factor receptor. This receptor is the gateway to a number of molecular pathways which regulate the ability of cancer cells to grow and relocate in the body, critical processes in the spread of cancer. K-ras is an oncogene which functions downstream of this receptor. When mutated, K-ras can bypass the action of Cetuximab, communicating with cancer cells to continue to grow.
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| Recent clinical trials have shown that patients with a mutation in the K-ras gene will not respond to Cetuximab. However, if K-ras is not mutated, significant response is observed when the drug is administered in combination with standard chemotherapy (FOLFIRI). “This marks a significant advance in the treatment of advanced bowel cancer, not only for the 60% of patients whose cancer does not have a mutation in K-ras, but also for the remaining patients who will be offered an alternate therapy more likely to work” said Dr Whitehall. “I am very excited about the introduction of this test, as it represents the first step towards personalised medicine for patients with advanced bowel cancer”. | Macroscopic, microscopic and molecular features are shown for a ‘serrated pathway’ polyp (top panel) and a ‘traditional pathway’ polyp (bottom panel). Serrated pathway polyps are typically flat and more easily visualised using magnifying, dye-spray colonoscopy (A). They have a distinctive serrated-appearing morphology (B) and frequently have mutation of the BRAF oncogene, detected here using an allelic discrimination assay (C). Tubular adenomas are the precursor of the traditional pathway and often grow on a ‘stalk’ of normal tissue, which simplifies colonoscopic resection (D). These adenomas have a strikingly different histological appearance (E) compared to serrated polyps and do not have BRAF mutations, but may show mutation of the K-ras oncogene, detected here using high resolution melt analysis (F). | |||
