ABC transporters in anticancer drug transport ? Lessons for Therapy, Drug Development and Delivery Systems

The structural aspects as well as the classification of the ABC superfamily (the largest group of transmembrane proteins) has been highlighted. Over-expression of one or more of these transporters, barring exceptions, can correlate with an increased drug resistance (the multidrug resistance phenotype). Hence, studying these proteins, using experimental and in silico approaches, has tremendous benefit for patient selection as well as stratification into “good” and “poor” drug responders. Further, the need to obtain a better insight into “intrinsic” and “extrinsic” mechanisms of resistance were reiterated upon, based on the relative recruitment of the different signal transduction molecules. The concept of the reversal of the MDR phenotype, has been discussed and extended in the context of combination therapy. This form of therapy involves the use of a cocktail of synthetic and biopharmaceutical drugs as well as nanotechnology-based approaches, for improvements in their pharmacokinetic (PK) and pharmacodynamic (PD) profile. Such strategies have targeted the heterogeneous cancer and cancer stem cells, signaling molecules, marker enzymes as well as the microenvironment for improved efficacy and safety as well as to minimize the chance of relapse

Author(s): Suresh P.K, Vembuli Amman Varadharaj, Jayasindu Mathiyazhagan

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