Term
| binds to Topo I making a cleavable complex (drug, DNA and Topo I) which in turn causes single strand breaks to the DNA |
|
Definition
|
|
Term
| Irinotecan has activity against a variety of malignancies |
|
Definition
| colorectal cancer; small cell lung cancer |
|
|
Term
| Irinotecan has significant side effects in 20-35% of patients |
|
Definition
| diarrhea, neutropenia, and vascular syndromes |
|
|
Term
| irinotecan --> inactive metabolize |
|
Definition
|
|
Term
|
Definition
|
|
Term
| highly potent active metabolite (the reason for pharmacological action of irinotecan and antitumor activity) |
|
Definition
|
|
Term
| once SN-38 works at the tumor level |
|
Definition
| gets eliminated in the bile after glucuronidation |
|
|
Term
| result of 7 TA repeats in the promoter region instead of 6 repeats (wild type) |
|
Definition
|
|
Term
| reduced gluronidation activity: associated with reduced clearance of SN-38 (results in toxic effects) |
|
Definition
|
|
Term
| associated with hyperbilirubinemia (Gilbert's Syndrome) |
|
Definition
| increased concentration of active SN-38 metabolite |
|
|
Term
| highest in Asian (76), Caucasians (46), and African American (26) |
|
Definition
|
|
Term
| highest in Caucasians (39), Afrian American (37), Asian (2) |
|
Definition
|
|
Term
| highest in African American (19), Caucasian (13), and Asian (5) |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| FDA approved on august 2005, 100% accuracy compared to DNA sequencing; processing time of 4-5 hours; several commercial tests are now available |
|
Definition
| Invader UGT1A1 Molecular Assay |
|
|
Term
| only 30-40% of these patients suffer severe toxicities, dose reduction may result in decreased efficacy; prospective dosing trial needs to be confirmed or denied |
|
Definition
|
|
Term
| max tolerated dose for UGT1A1 wild type |
|
Definition
|
|
Term
| max tolerated dose for UGT1A1 heterozygote |
|
Definition
|
|
Term
| max tolerated dose for UGT1A1 homozygous variant |
|
Definition
|
|
Term
| significantly higher risk of severe neutropenia and possible high risk of diarrhea; HOWEVER reduced dose may also compromise the efficacy of therapy! |
|
Definition
| patient homozygous for UGT1A1*28 |
|
|
Term
| monoclonal antibodies currently approved to treat metastatic colorectal cancer |
|
Definition
|
|
Term
|
Definition
| bind to extracellular EGFR domain leading to inhibition of downstream signaling |
|
|
Term
| thought to control cell growth, differentiation and apoptosis |
|
Definition
| the KRAS signaling pathway |
|
|
Term
| mutations that activate KRAS |
|
Definition
| result in activation of further downstream signaling pathways and allows RESISTANCE OF INHIBITION of cell surface receptor tyrosine kinases such as EGFR |
|
|
Term
| 27-43% in tumor samples collected from colorectal cancer patients across 7 trials |
|
Definition
| prevalence of mutated KRAS |
|
|
Term
| if you have an expression of receptor but have mutation in the KRAS gene |
|
Definition
| will not benefit from inhibiting EGFR |
|
|
Term
| if the patient is wild type: inhibiting EGFR |
|
Definition
| is efficacious and would prevent cancerous overgrowth due to uncontrolled EGFR signaling |
|
|
Term
| colorectal cancer patients who tumor has a mutated KRAS |
|
Definition
| have a low likelihood of responded to anti-EGFR monoclonal antibody therapy |
|
|
Term
| Multiple commercial test kits available; tumor DNA extracted from tissue sample |
|
Definition
|
|
Term
| gold standard endocrine therapy for patients with ER+ or PR+ breast cancer |
|
Definition
|
|
Term
|
Definition
| considered a selective estrogen receptor modulator |
|
|
Term
| Tamoxifen ---> N-D-methylTAM |
|
Definition
|
|
Term
| N-D-methyl tam --> endoxifen |
|
Definition
|
|
Term
| very potent metabolite responsible for the in vivo pharmacologic activity of tamoxifen |
|
Definition
|
|
Term
| CYP2D6 enzyme (converts N-D-methyl TAM to Endoxifen) |
|
Definition
|
|
Term
| decreased enzyme activity |
|
Definition
|
|
Term
| loss (null) of enzyme activity |
|
Definition
|
|
Term
| increased enzyme activity |
|
Definition
|
|
Term
| the clinical presentation of an individual with a particular genotype |
|
Definition
|
|
Term
|
Definition
| possess 2 wild type alleles (normal metabolizer) |
|
|
Term
| intermediate metabolizers |
|
Definition
| 1 wild type allele and 1 variant allele (heterozygous) |
|
|
Term
|
Definition
| 2 variant alleles (homozygous variant) |
|
|
Term
| Caucasian (20-25), African American (6-7); Asian (1) |
|
Definition
|
|
Term
| Asian (35-55), Caucasian and African American (2-5) |
|
Definition
|
|
Term
| African American (10-43); Asian (2-5), Caucasian (<1%) |
|
Definition
|
|
Term
| decreased incidence in CYP2D6*4/*4 patients; variable incidence reported elsewhere in CYP2D6*4/*4 patient |
|
Definition
|
|
Term
| could switch to aromatase inhibitor (anastrazole, letrozole, exemestrane); possible dose increase but unproven benefit |
|
Definition
|
|
Term
| no proven alternatives to tamoxifen, possible dose increase |
|
Definition
|
|
Term
| presence of one of these alleles causes deficiency of TPMT, leading to decreased clearance of the inactive methylated metabolites and greater toxicity including myelosuppression and hepatotoxicity |
|
Definition
|
|
Term
| metabolized into 6-MP--> 6-thiurine via xanthine oxidase to an inactive metabolite |
|
Definition
|
|
Term
| 10% of Caucasians and African Americans |
|
Definition
| heterozygous resulting in intermediate TPMT activity |
|
|
Term
|
Definition
| homozygous resulting in low or absent TPMT activity |
|
|
Term
| most common allele in caucasians |
|
Definition
|
|
Term
| most common allele in Asians and African-Americans |
|
Definition
|
|
Term
| 80-90% reduction of initial dose |
|
Definition
| patients who are homozygous, and thus possess 2 variant TPMT alleles |
|
|
Term
| genotyping and phenotyping for TPMT SNPs |
|
Definition
|
|
