Current Clinical Practice: Application of Resistance Reversal Agents in Hematologic Malignancies

Abstract

The clinical application of resistance reversal drugs for patients with hematologic malignancies is reviewed. The phenomenon of multidrug resistance versus other mechanisms are discussed. The pump-like mechanisms of P-glycoprotein, multidrug resistance associated protein, lung resistance protein and of other ATP binding cassette transporter proteins are reviewed briefly, as well as the important substrate drugs and pump-blocking compounds. The problems associated with resistance protein assays in clinical samples and the concept of prognostic versus therapeutic clinical relevance are described, within the context of selected hematologic malignancies. Toxicities and treatment outcomes of phase II and III trials of reversal agents in lymphoma, multiple myeloma, myelodysplastic syndromes, acute myeloid leukemia and blast phase of chronic myeloid leukemia are reviewed. Finally, current options for on-study management of relapsed or refractory hematologic malignancy patients are discussed.

Keywords:

• Drug resistance
• P-gp
• MRP
• LRP