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New combination of genetic markers better identifies those that benefit from anticancer drug.
Posted On: September 30, 2016
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A clinical trial showed that targeted cetuximab therapy for colon cancer is possible: a genetic marker can be used to identify which patients benefit.
Patients with metastatic colorectal cancer may receive a medication called cetuximab as part of their treatment. However, only a portion of those patients benefit from the therapy, which is expensive and can have side effects.
Changes in a gene known as RAS have been found to identify patients that respond to cetuximab therapy. Around 40% of all patients have genetic changes in RAS that preclude them from receiving cetuximab. However, many patients that do receive the drug—despite favourable RAS status—experience little therapeutic benefit from the therapy.
To improve how patients are selected for cetuximab therapy, PM Senior Scientist Dr. Geoffrey Liu and colleagues explored a different approach: they looked at tumour as well as healthy tissues from samples collected from patients enrolled in an international clinical trial. This approach identified, in the healthy tissue, small genetic changes in a gene for the Fc-ɣ receptor, which plays a role in the how cetuximab helps the body’s immune system identify tumour cells and attack them.
When combined, the two genetic readouts—Fc-ɣ in healthy tissue and RAS in the tumour—better identified which patients benefit from cetuximab. Use of the new Fc-ɣ receptor marker identified two thirds of those who would normally be selected for cetuximab as unlikely to benefit. Thus, the new screening method has the potential to greatly improve the selection of patients for treatment, while ensuring that only those that will benefit receive the drug.
See Dr. Liu talk about the study in an interview with UHN Public Affairs here.
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]
Changes in a gene known as RAS have been found to identify patients that respond to cetuximab therapy. Around 40% of all patients have genetic changes in RAS that preclude them from receiving cetuximab. However, many patients that do receive the drug—despite favourable RAS status—experience little therapeutic benefit from the therapy.
To improve how patients are selected for cetuximab therapy, PM Senior Scientist Dr. Geoffrey Liu and colleagues explored a different approach: they looked at tumour as well as healthy tissues from samples collected from patients enrolled in an international clinical trial. This approach identified, in the healthy tissue, small genetic changes in a gene for the Fc-ɣ receptor, which plays a role in the how cetuximab helps the body’s immune system identify tumour cells and attack them.
When combined, the two genetic readouts—Fc-ɣ in healthy tissue and RAS in the tumour—better identified which patients benefit from cetuximab. Use of the new Fc-ɣ receptor marker identified two thirds of those who would normally be selected for cetuximab as unlikely to benefit. Thus, the new screening method has the potential to greatly improve the selection of patients for treatment, while ensuring that only those that will benefit receive the drug.
See Dr. Liu talk about the study in an interview with UHN Public Affairs here.
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]