1.Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy.
Yu QQ1, Qiu H1, Zhang MS1, Hu GY1, Liu B1, Huang L1, Liao X1, Li QX1, Li ZH1, Yuan XL1. World J Gastroenterol. 2016 Apr 28;22(16):4250-8. doi: 10.3748/wjg.v22.i16.4250.
AIM: To examine the predictive effects of baseline serum bilirubin levels and UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism on response of colorectal cancer to irinotecan-based chemotherapy.
2.A Randomized, Phase II Trial of Cetuximab With or Without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients With Metastatic Colorectal Carcinoma.
Bowles DW1, Kochenderfer M2, Cohn A3, Sideris L4, Nguyen N5, Cline-Burkhardt V6, Schnadig I7, Choi M8, Nabell L9, Chaudhry A10, Ruxer R11, Ucar A12, Hausman D13, Walker L13, Spira A14, Jimeno A15. Clin Colorectal Cancer. 2016 Mar 31. pii: S1533-0028(16)30029-9. doi: 10.1016/j.clcc.2016.03.004. [Epub ahead of print]
BACKGROUND: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase/mammalian target of rapamycin signaling pathway is frequently altered in colorectal cancer (CRC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. This randomized phase II study evaluated cetuximab with or without PX-866 in patients with metastatic, anti-epidermal growth factor receptor-naive, KRAS codon 12 and 13 wild-type CRC.
3.Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients.
Mbatchi LC1,2,3, Robert J4, Ychou M2,5, Boyer JC1, Del Rio M2, Gassiot M1,2, Thomas F6, Tubiana N7, Evrard A8,9,10. Clin Pharmacokinet. 2016 Apr 26. [Epub ahead of print]
BACKGROUND AND OBJECTIVES: Nuclear receptors PXR (pregnane X receptor, NR1I2) and CAR (constitutive androstane receptor, NR1I3) are key regulators of irinotecan metabolism, and ligand-dependent modulation of their activity leads to significant drug-drug interactions. Because genetic polymorphisms can also affect the activity of these xenobiotic-sensing receptors, we hypothesized that they could contribute to the interpatient variability of irinotecan pharmacokinetics and to the toxicity of irinotecan-based regimens.
4.The contribution of pharmacogenetics to pharmacovigilance.
Bondon-Guitton E1, Despas F2, Becquemont L3. Therapie. 2016 Mar-Apr;71(2):223-8. doi: 10.1016/j.therap.2016.02.005. Epub 2016 Mar 3.
Since the beginning of this century, information on pharmacogenetics appears in the summary of product characteristics (SPC) of drugs. Pharmacogenetic tests particularly concern the enzymes involved in the metabolism of drugs, among which P450 cytochromes. Some patients known as poor metabolisers eliminate some drugs more slowly, causing overdoses and adverse drug reactions (ADRs). The best-known examples are AVK and VKORC1-CYP2C9 or clopidogrel and CYP2C19. In the USA, the tests are recommended before the introduction of these drugs to prevent the occurrence of ADRs. Other tests are also commonly performed to address the toxicity of certain anticancer drugs (DPYD-capecitabine, UGT1A1-irinotecan, TPMT 6-mercaptopurine). Pharmacogenetic testing is also available to identify HLA loci that are very strongly associated with the occurrence of immuno-allergic reactions to a specific drug. The best-known example is HLA-B*5701, strongly associated with hypersensitivity to abacavir, and this test is now always prescribed before the instatement of this drug.