Pharmacogenomics uses knowledge about the genetic makeup or genome of a person to pick the drugs and doses of drugs that are likely to function best for that specific individual. The study of how medicines function, called pharmacology, blends this new discipline called genomics and this term collectively called as Pharmacogenomics.
Some drugs can work for you efficiently than they do in other individuals, depending on your genetic makeup. Similarly, some drugs in you can cause side effects than in someone else.
We help Doctors to choose the right drug to stop the trial-and-error method of offering you multiple medications that are not likely to work for you until they find the correct one by using knowledge about your genetic make-up. The “best-fit” drug to assist you can be picked from the beginning using our pharmacogenomics panels.
DPYD testing for Treatment with 5-fluorouracil treatment (10 Variants)
An enzyme known as dihydropyrimidine dehydrogenase (DPYD) is encoded by the DPYD gene. This enzyme is important for the metabolism of fluoropyrimidine drugs including fluorouracil/5-FU and capecitabine. For certain cancers, including head and neck, gastrointestinal and colorectal cancers, these medications are all part of chemotherapy treatment. As a result of reduced DPYD activity, mutations or variations in DPYD are known to cause significant 5-FU toxicity. Before beginning their treatment protocol, patients who are candidates for therapy with fluorouracil or capecitabine should be considered for DPYD genotyping, especially if the patients have a personal or family history of 5-FU toxicity.
UGT1A1 for Irinotecan therapy (3 variants)
UGTs play a major role in the conjugation and subsequent elimination of xenobiotics and endogenous compounds which are potentially toxic. A hepatic enzyme responsible for bilirubin conjugation encodes the UGT1A1 gene. It also acts on the active metabolite, the primary cause of treatment-related toxicity of chemotherapeutic agents including irinotecan, which is used in the treatment of colorectal and gastric cancers. The lengths in the promoter region of the UTG1A1 gene of the repeat polymorphism are determined using Sanger Sequencing by fragment analysis.
Glioblastoma IDH1 and IDH2 Mutations
In around 15-20 % of acute myeloid leukaemia (AML), IDH1 or IDH2 mutations are observed and grade II or III brain gliomas of > 70 percent. It is possible that patients with AML and mutations aggressive cancer, while glioma mutations are associated with improved prognosis. For patients with IDH1, long term survival after aggressive tumour resection has been confirmed beneficial astrocytomas. Bi-directional sequencing in both IDH1 and IDH2 of the hotspot regions of the exon 4 mutation. Genes IDH1 and IDH2 are analysed simultaneously. Testing can be done for haematological diseases to boost sensitivity which is being performed on plasma.
EGFR mutation detection in exon 18,19,20,21 in NSCLC for treatment with EGFR TKIs
There are mutations in the EGFR gene in about 25 % of non-small cell lung cancers (NSCLC). Most mutations in exons 18, 19, 20 and 21 occur in hotspot areas. Epidermal growth factor receptor (EGFR) gene mutations are biomarkers that predict how patients with non-small cell lung cancer (NSCLC) react to EGFR-targeted therapies known collectively as tyrosine kinase inhibitors (TKIs). EGFR genotyping therefore offers essential details for the decision on treatment. For EGFR genotyping Sanger sequencing is employed to identify the mutations in the exon regions.
Detection of T790M in EGFR in non-small-cell lung cancer (NSCLC)
The most common cause of death from cancer worldwide is lung cancer, there is non-small cell lung cancer (NSCLC) and 85-90 % of lung cancers. Presence of the epidermal growth cell receptor (EGFR) gene-driver mutations in a subset of non-small cell lung cancer NSCLC. The use of tyrosine kinase inhibitors (TKI) that inhibit EGFR signalling has led to the use of the pathway.
The epidermal growth factor receptor (EGFR) gene has been identified as a non-small cell lung cancer (NSCLC) driving gene, and the efficacy of the EGFR-tyrosine kinase (TKI) inhibitor has been demonstrated, but acquired resistance is inevitable. The presence of T790M-mutation will recognise patients who are eligible for tyrosine kinase inhibitor (TKI) therapy.
Tumours that contain such EGFR mutations may have an initial response. EGFR-TKIs, however many develop post-treatment resistance mutations, also at exon 20’s amino acid position 790 (T790 M). Accurate detection of T790M in patients whose disease progressed on initial TKI therapy is thus vital for subsequent management.
Variants in PIK3CA (Exon7, 9, 20)
A significant cell signalling pathway mediating cell proliferation and survival is the phosphatidylinositol 3-kinase / AKT axis, two biological processes that control the growth of malignant cells. The p110α subunit of the phosphatidylinositol 3-kinase protein encodes the phosphatidylinositol 3-kinase CA gene. In some types of human tumours, there are phosphatidylinositol 3-kinase CA mutations, and they are commonly seen in breast cancer. In a broad variety of tumours, including glioblastoma, gastric cancer, lung cancer, ovarian cancer, hepatocellular cancer, endometrial cancer, brain cancer and breast cancer, this gene is mutated. Phosphatidylinositol 3-kinase CA mutations are associated with poor survival and may be useful biomarkers for the detection of aggressive tumour patients with breast cancer and for the prediction of response to PI3K pathway inhibitor therapy.
Detection of BRAFV600E and V600K mutations in Melanoma
In 7% of human cancers, BRAF mutations were detected. They are uncommon in certain tumours, such as myeloma (4%) and are present in 100% of hairy cell leukaemia. The prevalence of BRAF mutations in melanoma is 40% to 50% and depends on the form of melanoma. A substitution of glutamic acid for valine at codon 600 BRAF protein, is the most common mutation found in about 75% of all BRAF mutation-positive melanoma (V600E).
Detection of ABL Kinase mutations for drug response (Exon 4, 5, 6,7)
Chronic myeloid leukaemia (CML), the myeloproliferative disorders are better characterised and are associated with the development of myeloproliferative disorders in over 95% of the affected patients. The BCR-ABL1 is a fusion oncogene, the product of the chromosomal translocation of t(9;22)(9q34.1)(22q11.2). The BCR-ABL gene and the fusion protein that has the activity of constitutive tyrosine kinase result from this translocation. The key cause of resistance to tyrosine kinase (TKIs) in patients with chronic myeloid leukaemia is mutations in the BCR-ABL tyrosine kinase domain in 30% to 90% of patients who develop resistance. Imatinib is a highly effective therapy in all stages of chronic myelogenous leukaemia (CML), but relapse after initial response is normal in patients with advanced disease. BCR-ABL kinase domain (KD) mutations have been observed in 50 to 90 % of patients with acquired resistance to imatinib. These mutations result in impaired binding of drugs and are believed to trigger clinical resistance.
Detection of variants in TPMT (TPMT2*, TPMT3A*TPMT3C*)
A phase two drug-metabolizing enzyme produced in the kidney, red blood cells, liver, and other tissues is thiopurine methyltransferase (TPMT). In the removal of thiopurine medicines, like mercaptopurine, azathioprine and thioguanine, TPMT plays a function. These medicines are usually used to treat acute lymphoblastic leukaemia, autoimmune disorders, inflammatory bowel disease and rejection of organ transplants. There is intermediate TPMT operation in about 10 percent of the population.
Life-threatening myelosuppression, a disorder in which bone marrow production is reduced, and other toxicities may be caused by impaired TPMT function in patients given regular thiopurine doses. In infants, impaired function has also been associated with ototoxicity caused by cisplatin, although this is not well known. To tolerate therapy and reduce the risk of adverse reactions, individuals with reduced TPMT activity may require thiopurine dose reductions of 50 to 90 percent.