Temozolomide resistance and tumor recurrence: Halting the Hedgehog

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dc.contributor.authorMunoz, Jessian L.
dc.contributor.authorRodriguez-Cruz, Vivian
dc.contributor.authorWalker, Nykia
dc.contributor.authorGreco, Steven J.
dc.contributor.authorRameshwar, Pranela
dc.date.accessioned2022-03-24T17:42:32Z
dc.date.available2022-03-24T17:42:32Z
dc.date.issued2015-05-07
dc.description.abstractChemotherapy with Temozolomide (TMZ), radiation and surgery are the primary methods to treat Glioblastoma Multiforme (GBM), the most common adult intracranial tumor with dismal outcome. GBM resistance to therapy is the main reason of poor patient outcomes. Thus, methods to overcome the resistance are an area of extensive research. This highlight focuses on three recently published articles on the mechanism of resistance and possible therapeutic intervention, including RNA treatment with stem cells. We showed a crucial role of the developmental Sonic Hedgehog (SHH) pathway in the acquisition and maintenance of TMZ resistance. SHH signaling caused TMZ resistance in GBM cells through an increase in the multiple drug resistance gene (MDR1). The SHH receptor, Patched-1 (PTCH1), negatively regulate SHH signaling. In GBM, miR-9 suppressed PTCH1 levels, resulting in the activation of SHH pathway. Thus, SHH signaling is independent of the ligand in resistant GBM cells. MiR-9 was also increased in chemoresistance CD133+ GBM cells. A potential method to reverse resistance was tested by delivering the anti-miR in bone marrow-derived Mesenchymal Stem Cells (MSCs). The anti-miR-9 was transferred into the resistant GBM cells through exosomes and gap junctional intercellular communication. We also review on-going clinical trials with inhibitor of SHH signaling, and also discuss drug delivery by cell therapy for GBM. While GBM treatment has proven to be a challenge, there are a number of novel approaches we are currently developing to manage this malignancy.en_US
dc.description.sponsorshipGrant support R01 CA089868/CA/NCI NIH HHS/United Statesen_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856152/en_US
dc.format.extent9 pagesen_US
dc.genrejournal articlesen_US
dc.genrepostprintsen_US
dc.identifierdoi:10.13016/m2l5uo-ra6i
dc.identifier.citationMunoz, Jessian L et al. “Temozolomide resistance and tumor recurrence: Halting the Hedgehog.” Cancer cell & microenvironment vol. 2,2 (2015): e747. doi:10.14800/ccm.747en_US
dc.identifier.urihttp://hdl.handle.net/11603/24417
dc.language.isoen_USen_US
dc.publisherCancer cell & microenvironmenten_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.en_US
dc.subjectGlioblastoma Multiforme (GBM)en_US
dc.subjectGBM resistance to therapyen_US
dc.subjectRNA treatment with stem cellsen_US
dc.subjectSonic Hedgehog (SHH) pathwayen_US
dc.subjectSHH signalingen_US
dc.titleTemozolomide resistance and tumor recurrence: Halting the Hedgehogen_US
dc.typeTexten_US
dcterms.creatorhttps://orcid.org/0000-0001-7603-9276en_US

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