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  1. Article ; Online: Penetrating the brain tumor space with DNA damage response inhibitors.

    Bindra, Ranjit S

    Neuro-oncology

    2020  Volume 22, Issue 12, Page(s) 1718–1720

    MeSH term(s) Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; DNA Damage ; Glioblastoma ; Humans ; Phthalazines ; Piperazines ; Temozolomide
    Chemical Substances Phthalazines ; Piperazines ; olaparib (WOH1JD9AR8) ; Temozolomide (YF1K15M17Y)
    Language English
    Publishing date 2020-11-29
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2028601-6
    ISSN 1523-5866 ; 1522-8517
    ISSN (online) 1523-5866
    ISSN 1522-8517
    DOI 10.1093/neuonc/noaa228
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5307: Show issues Location:
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  2. Article ; Online: Introduction: Progress Towards Genomically-directed Radiosensitization.

    Gupta, Gaorav P / Bindra, Ranjit S

    Seminars in radiation oncology

    2021  Volume 32, Issue 1, Page(s) 1–2

    Abstract: Radiation therapy continues to break down technological barriers to deliver ionizing radiation with exceptional anatomical precision. However, some tumor types and subtypes exhibit intrinsic biological resistance to radiotherapy, which can result in ... ...

    Abstract Radiation therapy continues to break down technological barriers to deliver ionizing radiation with exceptional anatomical precision. However, some tumor types and subtypes exhibit intrinsic biological resistance to radiotherapy, which can result in unsuccessful tumor eradication or symptom palliation. Radiation resistance can result from alterations in diverse genetic, epigenetic, and metabolic pathways. Therapeutic targeting of these tumor-specific alterations may provide tumor-selective radiosensitization with relative sparing of adjacent normal tissues. This issue of Seminars in Radiation Oncology presents a series of articles that describe recent progress towards genomically-directed radiosensitization.
    MeSH term(s) Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/radiotherapy ; Radiation Oncology ; Radiation Tolerance ; Radiation, Ionizing
    Language English
    Publishing date 2021-12-03
    Publishing country United States
    Document type Editorial
    ZDB-ID 1146999-7
    ISSN 1532-9461 ; 1053-4296
    ISSN (online) 1532-9461
    ISSN 1053-4296
    DOI 10.1016/j.semradonc.2021.09.009
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    Zs.A 3654: Show issues Location:
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  3. Article ; Online: Oncometabolites as Regulators of DNA Damage Response and Repair.

    Gueble, Susan E / Bindra, Ranjit S

    Seminars in radiation oncology

    2021  Volume 32, Issue 1, Page(s) 82–94

    Abstract: Dysregulation of DNA damage response and repair (DDR) contributes to oncogenesis, yet also generates the potential for targeted cancer therapies by exploiting synthetic lethal interactions. Oncometabolites, small intermediates of metabolism overproduced ... ...

    Abstract Dysregulation of DNA damage response and repair (DDR) contributes to oncogenesis, yet also generates the potential for targeted cancer therapies by exploiting synthetic lethal interactions. Oncometabolites, small intermediates of metabolism overproduced in certain cancers, have emerged as a new mechanism of DDR modulation through their effects on multiple DNA repair pathways. Increasing evidence suggests that oncometabolite-induced DDR defects may offer the opportunity for tumor-selective chemo- and radio-sensitization. Here we review the biology of oncometabolites and diverse mechanisms by which they impact DDR, with a focus on emerging therapeutic strategies and ongoing clinical trials targeting oncometabolite-induced DDR defects in cancer.
    MeSH term(s) DNA Damage ; DNA Repair ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/radiotherapy
    Language English
    Publishing date 2021-12-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1146999-7
    ISSN 1532-9461 ; 1053-4296
    ISSN (online) 1532-9461
    ISSN 1053-4296
    DOI 10.1016/j.semradonc.2021.09.004
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  4. Article ; Online: Polymer nanocarriers for targeted local delivery of agents in treating brain tumors.

    Josowitz, Alexander D / Bindra, Ranjit S / Saltzman, W Mark

    Nanotechnology

    2022  Volume 34, Issue 7

    Abstract: Glioblastoma (GBM), the deadliest brain cancer, presents a multitude of challenges to the development of new therapies. The standard of care has only changed marginally in the past 17 years, and few new chemotherapies have emerged to supplant or ... ...

    Abstract Glioblastoma (GBM), the deadliest brain cancer, presents a multitude of challenges to the development of new therapies. The standard of care has only changed marginally in the past 17 years, and few new chemotherapies have emerged to supplant or effectively combine with temozolomide. Concurrently, new technologies and techniques are being investigated to overcome the pharmacokinetic challenges associated with brain delivery, such as the blood brain barrier (BBB), tissue penetration, diffusion, and clearance in order to allow for potent agents to successful engage in tumor killing. Alternative delivery modalities such as focused ultrasound and convection enhanced delivery allow for the local disruption of the BBB, and the latter in particular has shown promise in achieving broad distribution of agents in the brain. Furthermore, the development of polymeric nanocarriers to encapsulate a variety of cargo, including small molecules, proteins, and nucleic acids, have allowed for formulations that protect and control the release of said cargo to extend its half-life. The combination of local delivery and nanocarriers presents an exciting opportunity to address the limitations of current chemotherapies for GBM toward the goal of improving safety and efficacy of treatment. However, much work remains to establish standard criteria for selection and implementation of these modalities before they can be widely implemented in the clinic. Ultimately, engineering principles and nanotechnology have opened the door to a new wave of research that may soon advance the stagnant state of GBM treatment development.
    MeSH term(s) Humans ; Polymers ; Drug Delivery Systems/methods ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Brain Neoplasms/pathology ; Glioblastoma/metabolism
    Chemical Substances Polymers ; Antineoplastic Agents
    Language English
    Publishing date 2022-12-02
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1362365-5
    ISSN 1361-6528 ; 0957-4484
    ISSN (online) 1361-6528
    ISSN 0957-4484
    DOI 10.1088/1361-6528/ac9683
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  5. Article ; Online: The Role of PARP Inhibitors in Patients with Primary Malignant Central Nervous System Tumors.

    Gueble, Susan E / Vasquez, Juan C / Bindra, Ranjit S

    Current treatment options in oncology

    2022  Volume 23, Issue 11, Page(s) 1566–1589

    Abstract: Opinion statement: Primary malignant central nervous (CNS) tumors are a devastating group of diseases with urgent need for improved treatment options. Surgery, radiation, and cytotoxic chemotherapy remain the primary standard treatment modalities, with ... ...

    Abstract Opinion statement: Primary malignant central nervous (CNS) tumors are a devastating group of diseases with urgent need for improved treatment options. Surgery, radiation, and cytotoxic chemotherapy remain the primary standard treatment modalities, with molecularly targeted therapies having proven efficacy in only small subsets of cases. Poly(ADP-ribose) polymerase (PARP) inhibitors, which have had immense success in the treatment of extracranial cancers with homologous recombination deficiency (HRD), are emerging as a potential targeted treatment for various CNS tumors. Although few primary CNS tumors display canonical BRCA gene defects, preclinical evidence suggests that PARP inhibitors may benefit certain CNS tumors with functional HRD or elevated replication stress. In addition, other preclinical studies indicate that PARP inhibitors may synergize with standard therapies used for CNS tumors including radiation and alkylating agents and may prevent or overcome drug resistance. Thus far, initial clinical trials with early-generation PARP inhibitors, typically as monotherapy or in the absence of selective biomarkers, have shown limited efficacy. However, the scientific rationale remains promising, and many clinical trials are ongoing, including investigations of more CNS penetrant or more potent inhibitors and of combination therapy with immune checkpoint inhibitors. Early phase trials are also critically focusing on determining active drug CNS penetration and identifying biomarkers of therapy response. In this review, we will discuss the preclinical evidence supporting use of PARP inhibitors in primary CNS tumors and clinical trial results to date, highlighting ongoing trials and future directions in the field that may yield important findings and potentially impact the treatment of these devastating malignancies in the coming years.
    MeSH term(s) Female ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Immune Checkpoint Inhibitors ; Ovarian Neoplasms/drug therapy ; Poly(ADP-ribose) Polymerases ; Central Nervous System Neoplasms/drug therapy ; Central Nervous System Neoplasms/etiology ; Biomarkers ; Alkylating Agents/therapeutic use
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors ; Immune Checkpoint Inhibitors ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Biomarkers ; Alkylating Agents
    Language English
    Publishing date 2022-10-15
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057351-0
    ISSN 1534-6277 ; 1527-2729
    ISSN (online) 1534-6277
    ISSN 1527-2729
    DOI 10.1007/s11864-022-01024-5
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    Zs.A 5523: Show issues Location:
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  6. Article ; Online: Intrathecal delivery and its applications in leptomeningeal disease.

    Khang, Minsoo / Bindra, Ranjit S / Mark Saltzman, W

    Advanced drug delivery reviews

    2022  Volume 186, Page(s) 114338

    Abstract: Intrathecal delivery (IT) of opiates into the cerebrospinal fluid (CSF) for anesthesia and pain relief has been used clinically for decades, but this relatively straightforward approach of bypassing the blood-brain barrier has been underutilized for ... ...

    Abstract Intrathecal delivery (IT) of opiates into the cerebrospinal fluid (CSF) for anesthesia and pain relief has been used clinically for decades, but this relatively straightforward approach of bypassing the blood-brain barrier has been underutilized for other indications because of its lack of utility in delivering small lipid-soluble drugs. However, emerging evidence suggests that IT drug delivery be an efficacious strategy for the treatment of cancers in which there is leptomeningeal spread of disease. In this review, we discuss CSF flow dynamics and CSF clearance pathways in the context of intrathecal delivery. We discuss human and animal studies of several new classes of therapeutic agents-cellular, protein, nucleic acid, and nanoparticle-based small molecules-that may benefit from IT delivery. The complexity of the CSF compartment presents several key challenges in predicting biodistribution of IT-delivered drugs. New approaches and strategies are needed that can overcome the high rates of turnover in the CSF to reach specific tissues or cellular targets.
    MeSH term(s) Animals ; Biological Transport ; Blood-Brain Barrier/metabolism ; Drug Delivery Systems ; Humans ; Immunotherapy ; Tissue Distribution
    Language English
    Publishing date 2022-05-10
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 639113-8
    ISSN 1872-8294 ; 0169-409X
    ISSN (online) 1872-8294
    ISSN 0169-409X
    DOI 10.1016/j.addr.2022.114338
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    Zs.A 2241: Show issues Location:
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  7. Article ; Online: Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma.

    Ganesa, Sachita / Sule, Amrita / Sundaram, Ranjini K / Bindra, Ranjit S

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 5827

    Abstract: The methylation status of the ... ...

    Abstract The methylation status of the O
    MeSH term(s) Antineoplastic Agents, Alkylating/pharmacology ; Antineoplastic Agents, Alkylating/therapeutic use ; Ataxia Telangiectasia Mutated Proteins/genetics ; Ataxia Telangiectasia Mutated Proteins/metabolism ; DNA Mismatch Repair/genetics ; DNA Modification Methylases/genetics ; DNA Modification Methylases/metabolism ; DNA Repair Enzymes/genetics ; DNA Repair Enzymes/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Humans ; Methyltransferases/metabolism ; Mismatch Repair Endonuclease PMS2/genetics ; MutL Protein Homolog 1/genetics ; MutL Protein Homolog 1/metabolism ; MutS Homolog 2 Protein/genetics ; Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Tumor Suppressor Proteins/metabolism
    Chemical Substances Antineoplastic Agents, Alkylating ; DNA-Binding Proteins ; Tumor Suppressor Proteins ; DNA Modification Methylases (EC 2.1.1.-) ; Methyltransferases (EC 2.1.1.-) ; MGMT protein, human (EC 2.1.1.63) ; ATR protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Mismatch Repair Endonuclease PMS2 (EC 3.6.1.3) ; MutL Protein Homolog 1 (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3) ; DNA Repair Enzymes (EC 6.5.1.-) ; Temozolomide (YF1K15M17Y)
    Language English
    Publishing date 2022-04-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-09614-x
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  8. Article ; Online: Use of stereotactic radiosurgery in treatment of brain metastases from pediatric extracranial solid tumors.

    Xu, Suzanne / Campbell, Allison / Chiang, Veronica / Bindra, Ranjit / Vasquez, Juan / Pashankar, Farzana

    Pediatric blood & cancer

    2023  Volume 70, Issue 7, Page(s) e30303

    MeSH term(s) Humans ; Child ; Radiosurgery ; Brain Neoplasms/pathology ; Retrospective Studies ; Treatment Outcome
    Language English
    Publishing date 2023-03-28
    Publishing country United States
    Document type Letter
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.30303
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    Zs.A 1131: Show issues Location:
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  9. Article ; Online: The Role of Mismatch Repair in Glioblastoma Multiforme Treatment Response and Resistance.

    Leelatian, Nalin / Hong, Christopher S / Bindra, Ranjit S

    Neurosurgery clinics of North America

    2021  Volume 32, Issue 2, Page(s) 171–180

    Abstract: Mismatch repair (MMR) is a highly conserved DNA repair pathway that is critical for the maintenance of genomic integrity. This pathway targets base substitution and insertion-deletion mismatches, which primarily arise from replication errors that escape ... ...

    Abstract Mismatch repair (MMR) is a highly conserved DNA repair pathway that is critical for the maintenance of genomic integrity. This pathway targets base substitution and insertion-deletion mismatches, which primarily arise from replication errors that escape DNA polymerase proof-reading function. Here, the authors review key concepts in the molecular mechanisms of MMR in response to alkylation damage, approaches to detect MMR status in the clinic, and the clinical relevance of this pathway in glioblastoma multiforme treatment response and resistance.
    MeSH term(s) Antineoplastic Agents, Alkylating/therapeutic use ; DNA Mismatch Repair/genetics ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Humans ; Temozolomide/therapeutic use
    Chemical Substances Antineoplastic Agents, Alkylating ; Temozolomide (YF1K15M17Y)
    Language English
    Publishing date 2021-02-18
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1196855-2
    ISSN 1558-1349 ; 1042-3680
    ISSN (online) 1558-1349
    ISSN 1042-3680
    DOI 10.1016/j.nec.2020.12.009
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  10. Article ; Online: The Higher the Grade, the Bigger the Field.

    Beckta, Jason M / Bindra, Ranjit S

    International journal of radiation oncology, biology, physics

    2018  Volume 102, Issue 3, Page(s) 488–489

    MeSH term(s) Female ; Humans ; Middle Aged ; Pineal Gland/pathology
    Language English
    Publishing date 2018-09-21
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2018.08.019
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