Genetic "Hotspots” Tailor Therapies for Bowel Cancer Treatment

A new study has identified the repetition frequency of new genetic "hotspots,” which could help doctors offer personalized therapies for bowel cancer patients.

Researchers at the University of Dundee (United Kingdom) carried out a genetic analysis on 106 bowel cancer tumor samples to search for the frequency of known faults in a key gene called K-Ras--an important protein which acts as an "on-off switch” in cells to control growth--since it is already known that in some bowel cancers the K-Ras gene is faulty, leaving the switch permanently "on.” The researchers screened the colorectal tumors for additional K-Ras mutation phenotypes and Ras guanine triphosphate (GTP)-ase activating assays and gene and pathway changes induced by individual K-Ras mutants.

The researchers found that besides the current K-Ras "hotspots” in codons 12, 13, and 61, four additional K-Ras mutations (Leu19Phe, Lys117Asn, Ala146Thr, and Arg164Gln) were identified, most commonly at codon 146. The researchers additionally identified a new K-Ras gene amplification event, present in approximately 2% of tumors. According to the researchers, the study suggests that as many as 33% of bowel cancer patients have a K-Ras fault. As a result, they recommend future mutation screening to facilitate optimal patient selection for treatment with Epidermal Growth Factor Receptor (EGFR)-targeted therapies should therefore be extended to codon 146, and in addition should consider the unique molecular signatures associated with individual K-Ras mutations. The study was published early online on February 9, 2010, in the British Journal of Cancer.

"These results highlight additional gene faults which potentially could be tested for in bowel cancer patients to determine which people will respond best to which drugs,” said lead author Gillian Smith, Ph.D. "The next stage is to develop effective tests to screen for these mutation 'hotspots' to help doctors to plan the most effective treatment strategies for bowel cancer patients - and this will encourage scientists to also focus their efforts on finding new treatments for patients with faulty K-Ras genes to give them more options.”

Targeted therapies are drugs that are designed to treat cancer cells while minimizing damage to normal, healthy cells. The drugs interfere with specific pathways involved in cancer cell growth or survival, such as blocking growth signals and reducing the blood supply to cancer cells; others stimulate the immune system to recognize and attack the cancer cell. The two types of targeted therapy that are currently being used for colorectal cancer are EGFR inhibitors--such as panitumumab, a monoclonal antibody that binds to and blocks EGFR--and antiangiogenic drugs.

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