Naema Nayyar
A5025986307- Brain Metastases and Treatment
- Glioma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Radiopharmaceutical Chemistry and Applications
- Click Chemistry and Applications
- Ferroptosis and cancer prognosis
- Synthesis and Biological Evaluation
- Advanced Breast Cancer Therapies
- Meningioma and schwannoma management
- Cancer therapeutics and mechanisms
- Immune cells in cancer
- CNS Lymphoma Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
- Barrier Structure and Function Studies
- Cancer Genomics and Diagnostics
- Neurofibromatosis and Schwannoma Cases
- Melanoma and MAPK Pathways
- Neuroblastoma Research and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Lymphoma Diagnosis and Treatment
- Bone Tumor Diagnosis and Treatments
- Peptidase Inhibition and Analysis
- Head and Neck Surgical Oncology
Massachusetts General Hospital
2015-2024
MGH Institute of Health Professions
2024
Harvard University
2015-2023
Center for Cancer Research
2019-2023
Broad Institute
2015-2023
University of Massachusetts Chan Medical School
2020-2023
Ludwig-Maximilians-Universität München
2023
Woman's Hospital
2023
German Cancer Research Center
2023
University of Tübingen
2023
We recently reported that BRAF V600E is the principal oncogenic driver of papillary craniopharyngioma, a highly morbid intracranial tumor commonly refractory to treatment. Here, we describe our treatment man age 39 years with multiply recurrent craniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, daily). After 35 days treatment, volume was reduced by 85%. Mutations mediate resistance MAPK pathway inhibition were not detected in post-treatment sample whole exome...
Abstract Purpose: Patients with KRAS-mutant non–small cell lung cancer (NSCLC) brain metastases (BM) have a poor prognosis. Adagrasib (MRTX849), potent oral small-molecule KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. has been optimized for favorable pharmacokinetic properties, including long half-life (∼24 hours), extensive tissue distribution, dose-dependent pharmacokinetics, central nervous system penetration; however, BM-specific...
Patients with meningiomas have widely divergent clinical courses. Some entirely recover following surgery alone, while others relentless tumor recurrences. This conundrum is exemplified by rhabdoid meningiomas, which are designated in the World Health Organization Classification of Tumours as high grade, despite only a subset an aggressive course. Patient management decisions further exacerbated rates interobserver variability, biased against missing possibly tumors. Objective molecular...
The blood-brain barrier (BBB) is modified to a blood-tumor (BTB) as brain metastasis develops from breast or other cancers. We (i) quantified the permeability of experimental metastases, (ii) determined composition BTB, and (iii) identified which elements BTB distinguished metastases lower those with higher permeability.A SUM190-BR3 inflammatory cancer subline was established. Experimental this model system two previously reported models (triple-negative MDA-231-BR6, HER2+ JIMT-1-BR3) were...
Abstract Brain metastases are devastating complications of cancer. The blood–brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood–tumor (BTB) when brain form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy limiting drug uptake. Here, we report that experimental breast cancer low- high permeability dextran dye exhibit distinct microenvironmental gene expression patterns. Astrocytic...
Abstract The genetic alterations that define primary central nervous system lymphoma (PCNSL) are incompletely elucidated, and the genomic evolution from diagnosis to relapse is poorly understood. We performed whole-exome sequencing (WES) on 36 PCNSL patients targeted MYD88 a validation cohort of 27 patients. also WES phylogenetic analysis 3 matched newly diagnosed relapsed tumor specimens 1 synchronous intracranial extracranial relapse. Immunohistochemistry (IHC) for programmed death-1...
Abstract Background Activating mutations in the pathway of phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target rapamycin (mTOR) occur 43–70% breast cancer brain metastasis patients. To date, treatment these patients presents an ongoing challenge, mainly because lack targeted agents that are able to sufficiently penetrate blood–brain barrier. GDC-0068 is a pan-Akt inhibitor has shown be effective various preclinical tumor models as well clinical trials. The purpose this study was...
The interplay between the immune system and tumor progression is well recognized. However, current human breast cancer immunophenotyping studies are mostly focused on primary tumors with metastatic lesions remaining largely understudied. To address this gap, we examined exome-capture RNA sequencing data from 50 (PBTs) their patient-matched (METs) in brain, ovary, bone gastrointestinal tract. We used gene expression signatures as surrogates for infiltrating lymphocytes (TILs) compared TIL...
Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with poor prognosis and limited treatment options. We present single arm Phase II study of 18 patients LMD receiving combined ipilimumab nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point overall survival at 3 months (OS3). Secondary points include toxicity, cumulative time-to-progression months, progression-free survival. A Simon two-stage design used to compare null...
Abstract High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. harbor an immunosuppressive tumor microenvironment (TME) programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating efficacy pembrolizumab, PD-1 inhibitor, in cohort 25 evaluable patients recurrent progressive grade 3 meningiomas. The primary endpoint is...
<h3>Importance</h3> Leptomeningeal disease (LMD) is a devastating complication of cancer that frequently underdiagnosed owing to the low sensitivity cerebrospinal fluid (CSF) cytologic assessment, current benchmark diagnostic method. Improving may lead improved treatment decisions. <h3>Objective</h3> To assess whether cell-free DNA (cfDNA) analysis CSF be used diagnose LMD more accurately than analysis. <h3>Design, Setting, and Participants</h3> This study conducted in neuro-oncology clinic...
Leptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, incidence LMD has steadily increased due to therapeutics that have extended survival cancer patients, highlighting need for new interventions. To examine efficacy immune checkpoint inhibitors (ICI) in patients LMD, we completed two phase II clinical trials. Here, investigate cellular molecular features underpinning...
Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently end stage of the disease. Immune checkpoint inhibitors (ICI) provide a opportunity against MBM; however, MBM tumor microenvironment (TME) has not been fully elucidated in context ICI. To dissect unique elements TME and correlates response to ICI, we collected 32 fresh performed single-cell RNA sequencing T-cell receptor clonotyping on T cells from matched blood...
Delays and risks associated with neurosurgical biopsies preclude timely diagnosis treatment of central nervous system (CNS) lymphoma other CNS neoplasms. We prospectively integrated targeted rapid genotyping cerebrospinal fluid (CSF) into the evaluation 70 patients lesions unknown cause. Participants underwent CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection single-nucleotide variants in MYD88, TERT promoter, IDH1, IDH2, BRAF, H3F3A genes...
Abstract Glioneuronal tumors constitute a histologically diverse group of primary central nervous system neoplasms that are typically slow-growing and managed conservatively. Genetic alterations associated with glioneuronal include BRAF mutations oncogenic fusions. To further characterize this tumors, we collected cohort 26 performed in-depth genomic analysis. We identified in (34%) fusions (30%), consistent previously published reports. In addition, discovered novel involving members the...
Immune checkpoint blockade has systemic efficacy in patients with metastatic melanoma, including those brain metastases (MBMs). However, immunotherapy-induced intracranial tumoral inflammation can lead to neurologic compromise, requiring steroids, which abrogate the of this approach. We investigated whether upfront neurosurgical resection MBM is associated a therapeutic advantage when performed prior initiation immunotherapy.
Nervous system injury is a frequent result of cancer therapy involving cranial irradiation, leaving patients with marked memory and other neurobehavioral disabilities. Here, we report an unanticipated link between bone marrow brain in the setting radiation injury. Specifically, demonstrate that marrow-derived monocytes macrophages are essential for structural functional repair mechanisms, including regeneration cerebral white matter improvement neurocognitive function. Using...
Papillary craniopharyngiomas are characterized by BRAFV600E mutations. Targeted therapy can elicit a dramatic radiographic regression of these tumors. Therefore, prediction BRAF mutation status before definitive surgery could enable neoadjuvant treatment strategies.To establish preoperative criteria to identify patients with mutant craniopharyngioma.Sixty-four craniopharyngioma were included in this study. We determined targeted sequencing. After scoring interobserver variability between...