An Alternative Indicator for Colon Cancer Patients

02/08/2016


Based on the work of Senior Scientist Dr. Geoffrey Liu, at the Princess Margaret Cancer Centre, and colleagues, there is now a more precise way for doctors to identify whether patients with metastatic colorectal cancer will benefit from a medication called cetuximab as part of their treatment.
 
Only a portion of patients who used cetuximab benefit from the expensive therapy, often dealing with side effects. Previously, these patients were identified through examining changes in a gene known as RAS. About 40% of all colorectal cancer patients cannot use cetuximab due to their genetic changes in the RAS gene. And out of the other 60% who are able to receive the drug, many won’t experience any therapeutic benefit.
 
That’s where Dr. Geoffrey Liu and his team come in. In order to advance patient selection for cetuximab therapy, the team looked at both tumor and healthy tissues samples collected from patients in an international clinical trial. This approach identified a new indicator in healthy tissue: small genetic changes found in a gene for the Fc-ɣ receptor. Genetic changes in this receptor play a role in how cetuximab helps the immune system to identify and attack tumor cells.
 
With this discovery, a new screening method was born: looking at both the Fc-ɣ genetic indicator and the RAS gene in the tumor as qualifying standards. This new method has allowed patients who will benefit from cetuximab therapy to be more accurately identified. In fact, the new Fc-ɣ receptor marker identified two thirds of patients unlikely to benefit from the treatment, all of who would have normally been selected to use cetuximab.  
 
This work was supported by the Ontario Institute for Cancer Research, Transgenomic Inc., the Canadian Institutes of Health Research, the Peter MacCallum Cancer Research Foundation and The Princess Margaret Cancer Foundation. Dr. G Liu holds the Alan B. Brown Chair in Molecular Genomics and the Cancer Care Ontario Chair in Experimental Therapeutics and Population Studies.
 
Fc-γ receptor polymorphisms, cetuximab therapy, and survival in the NCIC CTG CO.17 trial of colorectal cancer. Liu G, Tu D, Lewis M, Cheng D, Sullivan LA, Chen Z, Morgen E, Simes J, Price TJ, Tebbutt NC, Shapiro JD, Jeffery GM, Mellor JD, Mikeska T, Virk S, Shepherd LE, Jonker DJ, O'Callaghan CJ, Zalcberg JR, Karapetis CS, Dobrovic A. Clinical Cancer Research. doi 10.1158/1078-0432.CCR-15-0414. 2016 May 15. [Pubmed abstract]