Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.
Medulloblastoma is a diverse group of cerebellar tumors initiated from poorly differentiated neuroectodermal stem cells and characterized by the involvement of the genetic and epigenetic alterations in tumor development and treatment response (Aguilera et al., 2009; Hooper, Hawes, Kees, Gottardo, & Dallas, 2014). Four medulloblastoma subgroups that vary in their clinical outcome, age, gender, and molecular signatures have been identified (Hovestadt et al., 2019). These include; the WNT subgroup, comprising 10% of cases and characterized by the activation of the wingless-type signalling pathway (Jones et al., 2012); the sonic hedgehog (SHH) subgroup, which represents 20% of
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