Oncology
Personalized Medicine
Cancer care that is tailored to the genes and proteins in an individual’s tumour will help physicians to determine how best to treat it in each patient. Pharmacogenetic is a revolution in cancer care, bringing the concept of “personalized medicine” that promises to improve patient outcomes, avoid unnecessary treatments and, ultimately, reduce health care costs. The tests include:
• KRAS Mutation Test and B-RAF Mutation Test for Colorectal Cancer
• EGFR Mutation Test for Non-Small Cell Lung Cancer
• MGMT Methylation Test for Brain Cancer
KRAS Mutation Test and B-RAF Mutation Test for Colorectal Cancer:
• KRAS mutation test - for anti EGFR therapy
KRAS gene encodes a critical signaling protein in EGFR (Epidermal Growth Factor Receptor) pathway. KRAS mutation test can help doctors to prescribe appropriate anti EGFR drugs to the right patients first time around. DNA LAB has received certificate of participation in KRAS testing quality assessment scheme from European Society of Pathology KRAS EQA Scheme in molecular genetics.
KRAS facts
Up to 40% of colorectal cancer patients bear mutation in KRAS gene2. In opposition to normal KRAS, mutated KRAS renders cancer cells to undergo unregulated growth. More importantly, cancer patients with KRAS mutations are not responsive to targeted therapy against EGFR using cetuximab or panitumumab.
Recommendation from NCCN and ASCO (American Society of Clinical Oncologists) is that KRAS gene testing be part of the evaluation of patients with metastatic colorectal cancer. In addition, the United States FDA has recommended that cetuximab and panitumumab are to be given to patient with wild type KRAS only.
•B-RAF mutation test - for anti EGFR therapy
B-RAF gene is a downstream effector of K-RAS in the EGFR (Epidermal Growth Factor Receptor) pathway. KalGen provides B-RAF test which may serve as prognostic biomarker for colorectal and thyroid cancer patients.
B-RAF facts
Up to 40% of colorectal cancer patients bear mutation in K-RAS gene. In patient with normal K-RAS, up to 20% of patients may harbour B-RAF mutation has been shown to cause resistance to EGFR targeted therapy in preclinical studies.While clinical significance of B-RAF mutation as predictive factor to EGFR therapy is actively investigated, recent data suggests that B-RAF may serve as prognostic factor.
Colorectal cancer patient with B-RAF mutations seem to have poor prognosis than those who have normal B-RAF.B-RAF mutation is found in 50-70% of papillary thyroid cancer and associated with an aggressive tumour phenotype and higher risk or recurrent and persistent disease.In malignant melanoma, B-RAF mutation is found in around 60% of population. Unlike colorectal and thyroid cancer, B-RAF mutation in malignant melanoma tends to be associated with the better prognosis.
EGFR Mutation Test for Non-Small Cell Lung Cancer:
EGFR mutation test - for Tyrosine Kinase Inhibitors (TKIs) theraphy
Mutation in cytoplasmic domain for EGFR (Epidermal Growth Factor Receptor) causes over activated tyrosine kinase activity of the receptor. Targeted therapy drugs target this hyperactive kinase. Lung cancer patients with mutated EGFR have better response to tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib.
EGFR facts
Up to 60% non-smoking Asian women with non-small cell lung cancer (NSCLC) bear mutation of EGFR gene. This unique population get better response to tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib when given as first line therapy. Majority of EGFR mutation lies in exon 19 or exon 21, which cause EGFR to be more sensitive to TKIs. NSCLC patients with EGFR mutations are predicted to have good response to TKIs when given as first line therapy. Up to 60% on non-smoking Asian women patients have been found to harbour EGFR mutation. In contrast, EGFR mutation is found in less than 10% of Caucasian patients.
MGMT Methylation Test for Brain Cancer
MGMT methylation test – predictive or prognostic test for glioblastoma
MGMT is O-6 Methylguanine DNA methyltransferase which may either predict sensitivity to temozolomide or serve as prognostic factor when methylated in glioblastoma patients. Patients with methylated MGMT may gain maximum benefit of combined temozolomide and radiotherapy.
MGMT facts
MGMT is DNA repair gene that is causing chemotherapy resistance to temozolomide. However, patients with silenced MGMT due to methylation do gain benefit of temozolomide.
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