A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer

Abstract

Epirubicin 75 mg/m(2) and sulindac 600 mg are the recommended doses for phase II studies for these agents in combination.

Glioblastoma multiforme y estudio de la resistencia a la quimioterapia mediada por transportadores ABC

“…actualmente, existen inhibidores de alta selectividad para Mrp1, pero hasta ahora sólo sulindac ha sido demostrado ser seguro en estudios en fase clínica. Este fármaco está siendo evaluado en ensayos clínicos para la terapia conjunta con fármacos antitumorales en cáncer de mama y melanoma 28 , debido a que al igual que los gliomas de alto grado presentan la particularidad de tener una actividad de Mrp1 aumentada. También existen moléculas inhibidoras del transportador P-gp y que también pueden inhibir a Mrp1.…”

Cooperation between Prokaryotic (Lde) and Eukaryotic (MRP) Efflux Transporters in J774 Macrophages Infected withListeria monocytogenes: Studies with Ciprofloxacin and Moxifloxacin

“…This is so far undescribed, but reserpine has been shown to inhibit the transport of methotrexate (14), another known MRP substrate (17). The sharing of substrates and inhibitors among phylogenetically remote transporters is not a surprise since (i) most inhibitors act through a competitive mechanism (18,26,37), (ii) substrates can also be inhibitors (3,24), and (iii) common pharmacophores have been described for substrates and inhibitors of multidrug transporters (7,9). Further studies, however, will need to better characterize the properties common to the prokaryotic Lde and the eukaryotic MRP.…”

Drug resistance in cancer – searching for mechanisms, markers and therapeutic agents

“…Very few clinical circumvention studies have been conducted to combat the actions of other MDR pumps [6] , but the lessons of P-gp inhibitor trials suggest that effective use of such therapies will require better patient stratification based on in vivo characterisation of real pump activity levels.…”

“…Much resistancerelated research, therefore, both laboratory and clinical, has focused on reversing or circumventing resistance by inhibiting the activity of the efflux pumps [6] , or by treating resistant cells/tumours with drugs that are not substrates for the pump being overexpressed.…”