Surabhi Talele
University of Minnesota
PharmacodynamicsPharmacokineticsCancerInternal medicineDNA damageOncologyTransporterEfficacyIonizing radiationKnockout mouseEffluxIn vitroImmunohistochemistryIn vivoWild typePlaceboMdm2GlioblastomaSensitizationRadiosensitizerChemotherapyAntagonistAntibody-drug conjugateTemozolomideEGFR inhibitorsOsimertinibMelanomaErlotinibBlood–brain barrierDacomitinibBrain tumorEpidermal growth factor receptorDrug deliveryDrugVandetanibGefitinibAEE788Free fractionRegimenDepatuxizumab mafodotinStandard of careIn patientOptimal deploymentMedian survivalMolecular targetsBrain concentrationsProgrammed cell deathCancer researchRadiation therapyDNAFlow cytometryBioinformaticsSignal transductionDNA-PKcsMedicinePharmacologyDistribution (pharmacology)
9Publications
1H-index
16Citations
Publications 10
Newest
#1Sonja Dragojevic (Mayo Clinic)H-Index: 1
#2Ji Jianxiong (ZJU: Zhejiang University)
Last. Nicholas B. Remmes (Mayo Clinic)H-Index: 6
view all 15 authors...
Genotoxic damage induced by radiation triggers a highly coordinated DNA damage response (DDR), and molecular inhibitors of key nodes within this complex response network can provide profound enhancement in the anti-tumor efficacy of radiation. This is especially true for drugs targeting the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which is a core component of the non-homologous end-joining (NHEJ) DNA repair pathway, and Ataxia Telangiectasia mutated (ATM), which coordinates ...
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#1Danielle M. Burgenske (Mayo Clinic)H-Index: 2
#2Surabhi Talele (UMN: University of Minnesota)H-Index: 1
Last. Gautham Gampa (UMN: University of Minnesota)H-Index: 6
view all 22 authors...
BACKGROUND Glioblastoma (GBM) is an incurable disease with few approved therapeutic interventions. Radiation therapy (RT) and temozolomide (TMZ) remain the standards of care. The efficacy and optimal deployment schedule of the orally bioavailable small-molecule tumor checkpoint controller lisavanbulin alone, and in combination with, standards of care were assessed using a panel of IDH-wildtype GBM patient-derived xenografts. METHODS Mice bearing intracranial tumors received lisavanbulin +/- RT +...
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#1Bianca Maria Marin (Mayo Clinic)H-Index: 1
#2Kendra A Porath (Mayo Clinic)
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 30 authors...
BACKGROUND Antibody drug conjugates (ADCs) targeting the epidermal growth factor receptor (EGFR), such as depatuxizumab mafodotin (Depatux-M), is a promising therapeutic strategy for glioblastoma (GBM) but recent clinical trials did not demonstrate a survival benefit. Understanding the mechanisms of failure for this promising strategy is critically important. METHODS PDX models were employed to study efficacy of systemic vs intracranial delivery of Depatux-M. Immunofluorescence and MALDI-MSI wer...
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#1Jianxiong Ji (Mayo Clinic)
#2Emily L. Smith (Mayo Clinic)H-Index: 1
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 22 authors...
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#1Ann C. Mladek Tuma (Mayo Clinic)H-Index: 1
#2Shiv K. Gupta (Mayo Clinic)H-Index: 14
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 13 authors...
Robust function of the p53 tumor suppressor pathway is critical when treating with DNA-damage inducing agents such as radiation therapy (RT), which is a key component of standard care for GBM. MDM2 is an important negative regulator of p53 stability and MDM2 is amplified in approximately 14% of GBM. Based on the concept that suppression of MDM2 can reactivate p53 function and potentially have single agent or combinatorial effects, multiple MDM2 inhibitors have been developed. Here we report in v...
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#1Jianxiong Ji (Mayo Clinic)
#2Emily J. Smith (Mayo Clinic)H-Index: 1
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 15 authors...
Radio-resistant properties of melanomas undermine benefit of radiation therapy (RT). DNA-dependent protein kinase (DNA-PKcs) is essential for the non-homologous end joining (NHEJ) mediated repair DNA double-strand break (DSB). We evaluated radio-sensitizing effects of M3814, a selective oral inhibitor of DNA-PKcs, in patient-derived xenografts (PDXs) of melanoma brain metastases. M3814 (≥300 nM) inhibited RT-induced (5 Gy) auto-phosphorylation of serine-2056 of DNA-PKcs in primary cultures of M1...
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#1Gautham Gampa (UMN: University of Minnesota)H-Index: 6
#2Surabhi Talele (UMN: University of Minnesota)H-Index: 1
Last. William F. Elmquist (UMN: University of Minnesota)H-Index: 54
view all 6 authors...
Abstract Brain tumors are difficult to treat, in part, due to lack of adequate drug delivery across the blood–brain barrier (BBB). Although the BBB is compromised to some degree in brain tumors, it is not uniformly disrupted and some tumor locations have a relatively intact BBB. The presence of transporters (efflux) at the BBB limits the brain distribution of therapeutics intended for the treatment of CNS disorders. The differences in clearance processes, arising due to differences in the transp...
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#1Danielle M. Burgenske (Mayo Clinic)H-Index: 2
#2Ann C. Mladek (Mayo Clinic)H-Index: 19
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 18 authors...
Lisavanbulin (LIS; BAL101553) is the prodrug of BAL27862, a microtubule-binding, tumor checkpoint controller and potential radiosensitizer. These studies evaluated optimal integration of LIS with standard of care radiation therapy (RT) and/or temozolomide (TMZ) using GBM PDX models. Distribution across the blood brain barrier was evaluated after a single 30 mg/kg oral LIS dose, and concentrations of the active metabolite BAL27862 were measured by liquid chromatography-tandem mass spectrometry. S...
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#1Surabhi Talele (UMN: University of Minnesota)H-Index: 1
#2Afroz S. Mohammad (UMN: University of Minnesota)H-Index: 11
Last. William F. Elmquist (UMN: University of Minnesota)H-Index: 54
view all 7 authors...
Glioblastoma (GBM) is an aggressive and infiltrative primary brain tumor with a median survival of 14.6 months following the current treatment strategy of radiation and chemotherapy. Therefore, there is a need to develop strategies to enhance the efficacy of chemo-radiation treatments for GBM. DNA damage response signaling pathways play a critical role in DNA repair and cell survival following radiation therapy and the inhibition of these pathways could augment the cytotoxicity associated with r...
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#1Minjee Kim (UMN: University of Minnesota)H-Index: 6
#2Janice K. Laramy (UMN: University of Minnesota)H-Index: 7
Last. William F. Elmquist (UMN: University of Minnesota)H-Index: 54
view all 7 authors...
Tyrosine kinase inhibitors that target the epidermal growth factor receptor (EGFR) have had success in treating EGFR-positive tumors, including non–small-cell lung cancer (NSCLC). However, developing EGFR inhibitors that can be delivered to the brain remains a challenge. To identify optimal compounds for brain delivery, eight EGFR inhibitors [afatinib, 6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-(1-phenylethyl)-7H-pyrrolo[2,3-day]pyrimidin-4-amine (AEE788), [4-(3-chloro-2-fluoroanilino)-7-meth...
16 CitationsSource