Santosh Kesari

Santosh Kesari
John Wayne Cancer Institute · Neurosciences and Neurotherapeutics

MD, PhD

About

662
Publications
132,014
Reads
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26,667
Citations
Citations since 2016
281 Research Items
17508 Citations
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201620172018201920202021202205001,0001,5002,0002,5003,000
201620172018201920202021202205001,0001,5002,0002,5003,000
Additional affiliations
September 2009 - December 2015
University of California, San Diego
Position
  • Professor
January 2006 - December 2013
Brigham and Women's Hospital
January 2006 - December 2011
Beth Israel Deaconess Medical Center

Publications

Publications (662)
Article
Importance Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Pa...
Article
Full-text available
INTRODUCTION Virtual tumor board [VTB] platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. In order to deliver high-quality cancer care, it is necessary to coordinate numerous therapies and providers, and maintain open lines of communication among all professionals involved. Desi...
Article
We utilized the longitudinal clinical outcomes registry XCELSIOR (NCT03793088) to understand real world outcomes and treatment patterns among patients with diffuse midline glioma. A total of 74 patients were identified with a diagnosis of diffuse midline glioma by pathology or imaging (36 pediatric and 38 adult patients). Median age at diagnosis wa...
Article
INTRODUCTION Patients with leptomeningeal metastasis (LM) have limited treatment options and a poor outcome. However, they may benefit from targeted therapy. LM patients with HER2-positive primary breast cancer treated with IT trastuzumab demonstrated clinical benefit (Malani, 2020), and improved PFS (Figura, 2019). HER2 amplification in the primar...
Article
Despite current FDA approved treatments for glioblastoma (GBM), prognosis remains poor. The rare patient population and limited access to clinical trials are factors in this poor prognosis. Clinical trials need to increase enrollment of patients with glioblastoma and other brain cancers to more rapidly develop more effective treatments. Clinical tr...
Article
BACKGROUND Pineal parenchymal tumors of intermediate differentiation (PPTID) account for 21% to 54% of pineal parenchymal tumors and may be complicated by cerebrospinal dissemination (most commonly at time of reoccurrence; up to 4-10 years post resection). The integral membrane protein synaptophysin is expressed in neuroendocrine cells and virtuall...
Article
Glioblastoma (GBM) is the most common and aggressive primary brain tumor. External beam radiation therapy (EBRT) is widely recognized as an effective treatment for primary GBM. EBRT applied after GBM resection is associated with an increase in overall survival. Beyond upfront therapy with radiation and temozolomide chemotherapy, there is no standar...
Article
Glioblastoma is an aggressive disease with multiple disrupted signaling networks in the same tumor, demanding the development of personalized combination regimens. Using SYstems Genetics Network AnaLysis we analyzed TCGA multiomics datasets for 422 glioblastoma patients to generate a predictive disease network model (gbmSYGNAL). This model seeks to...
Article
INTRODUCTION ClinicalPath is an evidence-based oncology decision support and analytics tool for cancer care. ClinicalPath’s treatment recommendations are prioritized based on efficacy, toxicity, and cost by a nationwide committee of oncologists. The pathways are updated quarterly and are expected to speed the integration of new treatments into prac...
Article
Gliomas account for the vast majority of malignant primary tumors arising in the central nervous system. Elevated intracranial pressure (ICP) may be a potentially devastating complication of brain tumors and hydrocephalus. Brain tumors may occupy significant space causing displacement and compression of delicate structures within a finite intracran...
Article
BACKGROUND Metastatic involvement of the CSF by non-CNS neoplasms surpasses that of primary brain tumors, although conventional glioblastoma (GBM) can occasionally be identified in the CSF. Here, we apply Biocept’s CNSide test to examine a patient CSF sample with GBM, verified with an antibody against mutant p53. The p53 pathway is deregulated in 8...
Article
BACKGROUND Older age is a poor prognostic factor for glioblastoma (GBM) patients. We tested whether the intrinsic molecular landscape of the tumor may contribute to this poor prognosis. METHODS In accordance with the 2021 WHO classification scheme, we included only isocitrate dehydrogenase (IDH) wild type GBM. Based on published literature, we def...
Article
Background: Distinguishing between subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia in a scalable, accessible way is important to promote earlier detection and intervention. Objective: We investigated diagnostic categorization using an FDA-cleared quantitative electroencephalographic/event-related potential (qEEG...
Preprint
Full-text available
Background Vaccine immunotherapy may improve survival in GBM. A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing AV-GBM-1, (2) AE associated with AV-GBM-1 administration, and (3) survival. Methods Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM en...
Article
Full-text available
The increasing usage of smart wearable devices has made an impact not only on the lifestyle of the users, but also on biological research and personalized healthcare services. These devices, which carry different types of sensors, have emerged as personalized digital diagnostic tools. Data from such devices have enabled the prediction and detection...
Article
Full-text available
AdAPT-001 is an investigational therapy consisting of a replicative type 5 adenovirus armed with a TGF-β receptor-immunoglobulin Fc fusion trap, designed to neutralize isoforms 1 and 3 of the profibrotic and immunosuppressive cytokine, TGF-β. In preclinical studies with an immunocompetent mouse model, AdAPT-001 eradicated directly treated ‘cold’ tu...
Article
Full-text available
OBJECTIVE To report a summary of a systematic review of virtual tumor boards and their implementation in neuro- oncology. BACKGROUND Virtual tumor board [VTB] platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. VTBs are an emerging resource across various cancer care networks in...
Article
Full-text available
There is an unmet need to develop effective and tolerable treatments for pediatric patients with malignant central nervous system tumors. This is especially essential for pediatric patients with aggressive brain tumors such as high-grade gliomas which have a typical survival rate of under 2 years. Tumor Treating Fields (TTFields) are locoregional,...
Article
Bcl2-associated athanogene 3 (BAG3) is a multifunctional cochaperone responsible for protein quality control within cells. BAG3 interacts with chaperones HSPB8 and Hsp70 to transport misfolded proteins to the Microtubule Organizing Center (MTOC) and degrade them in autophagosomes in a process known as Chaperone Assisted Selective Autophagy (CASA)....
Article
Full-text available
Background The genomic and overall biologic landscape of glioblastoma (GB) has become clearer over the past two decades, as predictive and prognostic biomarkers of both de novo and transformed forms of GB have been identified. The oral chemotherapeutic agent temozolomide (TMZ) has been integral to standard-of-care treatment for nearly two decades....
Article
Standard aggressive therapy for primary newly diagnosed glioblastoma (GBM), which includes surgical resection followed by concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) and then maintenance TMZ, is associated with poor survival rates. Adding treatment with AV-GBM-1, a personal vaccine consisting of autologous dendritic cells (D...
Article
A major impediment to treatment of brain cancers is the inability to transport drugs across the blood-brain barrier (BBB). The development of an effective, targeted, and non-invasive method to penetrate the BBB to deliver cancer therapeutics is an unmet need in the treatment of brain cancers. Large molecular weight chemo- and immuno-therapies such...
Article
Full-text available
Background Virtual tumor board (VTB) platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. To deliver high-quality cancer care, it is necessary to coordinate numerous therapies and providers, share technical knowledge, and maintain open lines of communication among all professional...
Article
2019 Background: Gliomagenesis is regulated by dynamic epigenetic modifications of DNA methylation, deregulation of histones and alteration of the human Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes. These epigenetic genes are responsible for treatment resistance by inducing stemness of glioma cells and immune cells with i...
Article
e16245 Background: The proliferation of multi-omic diagnostics, highly selective targeted therapies, multi-modal immunotherapies, and personalized vaccines has yielded many promising novel combination regimens. Still, many patients with advanced cancer are left without clear options because the clinical efficacy of these regimens is based on anecdo...
Article
2056 Background: Capicua (CIC) Gene is a tumor suppressor, transcriptional repressor, and a member of the high mobility (HMG)-box protein family. CIC is a negative regulator of MAPK and RTK pathways; inactivating CIC mutations (mut) occur in approximately 40% of oligodendrogliomas (OLIG) and less frequently in other gliomas putatively activating do...
Preprint
Full-text available
Purpose xDECIDE is a clinical decision support system, accessed through a web portal and powered by a “Human-AI Team”, that offers oncology healthcare providers a set of treatment options personalized for their cancer patients, and provides outcomes tracking through an observational research protocol. This article describes the xDECIDE process and...
Article
Dysregulation of innate immune signaling pathways is implicated in various hematologic malignancies. However, these pathways have not been systematically examined in acute myeloid leukemia (AML). We report that AML hematopoietic stem and progenitor cells (HSPCs) exhibit a high frequency of dysregulated innate immune-related and inflammatory pathway...
Article
Background: There is great interest in finding ways to identify patients who will develop toxicity to cancer therapies. This has become especially pressing in the era of immune therapy, where toxicity can be long-lasting and life-altering, and primarily comes in the form of immune-related adverse effects (irAEs). Treatment with the first drugs in...
Article
Full-text available
Wearable devices use sensors to evaluate physiological parameters, such as the heart rate, pulse rate, number of steps taken, body fat and diet. The continuous monitoring of physiological parameters offers a potential solution to assess personal healthcare. Identifying outliers or anomalies in heart rates and other features can help identify patter...
Article
Full-text available
Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This re...
Article
A 2020 publication from Mahdavi and colleagues reported on clinical status changes observed among a sample of 31 older adults with neurodegenerative conditions who completed 12 months of bosutinib therapy. This abstract provides updated results for an additional 21 patients who have completed the 12‐month regimen since the time of the initial publi...
Article
Full-text available
WT2725 is a Wilms’ tumor gene 1 (WT1)-derived-oligopeptide vaccine designed to induce WT1-specific cytotoxic T-lymphocytes against WT1 ⁺ tumors in human leukocyte antigen (HLA)-A*0201 ⁺ and/or HLA-A*0206 ⁺ patients. Here, we report the results of a phase I study of WT2725. In this phase I, open-label, dose-escalation and expansion two-part study, t...
Article
A major impediment to treatment of brain cancers is the inability to transport drugs across the blood-brain barrier (BBB). The development of an effective, targeted, and non-invasive method to penetrate the BBB to deliver cancer therapeutics is an unmet need in the treatment of brain cancers. Large molecular weight chemo- and immuno-therapies such...
Article
INTRODUCTION Meningioma have an annual incidence of 5 per 100,000 and is the most frequent primary tumor of the central nervous system. Risk factors include radiotherapy and hormone intake. Most meningioma are grade I benign tumors, but up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological criteria. Extra-CNS metastasis is...
Article
BACKGROUND MDNA55 is an IL4R-targeted toxin in development for treatment of recurrent glioblastoma (rGBM). MDNA55 binds to IL4R expressed by tumor cells and non-malignant cells of the tumor microenvironment. METHOD MDNA55-05 was an open-label, single-arm study of MDNA55 delivered by CED as a single treatment in patients with 1st or 2nd recurrence...
Article
Full-text available
Despite treatment with radiation and temozolomide chemotherapy, malignant gliomas inevitably recur after treatment and have poor prognosis. Clinical trials should be offered when available, but effective treatment options for multiply recurrent tumors is sparse. In our multi-institutional retrospective cohort, we looked at recurrent malignant gliom...
Article
xCures operates a direct-to-patient, real-world evidence platform for decentralized clinical research. The platform leverages a nationwide observational research protocol (XCELSIOR, NCT03793088) to aggregate, normalize, and analyze N-of-1 clinical outcomes to continuously learn from and inform treatment decisions. Individual data elements are extra...
Article
In primary glioblastoma (GBM), overall survival (OS) is poor despite standard aggressive therapy. Adjunctive AV-GBM-1 vaccine immunotherapy may improve OS. In this multi-institutional phase II trial, key eligibility criteria for intent-to-treat (ITT) enrollment were: (1) primary GBM, (2) age < 70 years when GBM was resected, (3) successful GBM cell...
Article
Glioblastoma is the most common and aggressive primary brain tumor. Beyond upfront therapy with radiation and temozolomide chemotherapy there is no standard therapy that has been effective. Inhibitors of BRAF and MEK, a downstream protein immediately following BRAF, have been shown to have survival benefit for patients with other BRAF V600E mutant...
Article
Afatinib is a small molecule, selective and irreversible ErbB family blocker. In preclinical models it effectively inhibits EGFR, HER2 and HER4 phosphorylation resulting in tumor growth inhibition and is approved for the treatment of EGFR-mutated metastatic non-small cell lung carcinoma and metastatic squamous cell lung carcinoma. Pulse dosing afat...
Article
Background Standard aggressive therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with a 25% 2-year overall survival (OS). Adding treatment with AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed wi...
Article
Background Standard therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with poor overall survival (OS). Adding treatment with AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor...
Article
Background Despite standard aggressive therapy (maximum safe surgical resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ), then maintenance TMZ), 2-year survival is only about 25% for patients with newly diagnosed primary glioblastoma (GBM). Adding AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed w...
Article
Background Standard glioblastoma (GBM) therapy includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ), and maintenance TMZ, but it is associated with a 2-year survival of only about 25%. Adding treatment with AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor...
Article
Background For patients with newly diagnosed primary glioblastoma (GBM), maximum safe surgical resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ results in a 2-year survival of only 25%. Adding treatment with AV-GBM-1, a personal vaccine consisting of autologous dendritic cells (DC) pulsed wi...
Article
Background Despite standard aggressive therapy, including maximum safe surgical resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, survival is still extremely poor for patients with newly diagnosed primary glioblastoma (GBM). Adding treatment with AV-GBM-1, a personal vaccine consisting of au...
Article
Full-text available
Heretofore, there are no FDA-approved immunotherapeutics for malignant gliomas despite many novel therapies currently in different stages of clinical trials. Malignant gliomas are immunosuppressive tumors and are difficult for immune effector cells to infiltrate the tumor sites in the central nervous system. This inefficiency results in median surv...
Article
Full-text available
During morphogenesis, molecular mechanisms that orchestrate biomechanical dynamics across cells remain unclear. Here, we show a role of guidance receptor Plexin-B2 in organizing actomyosin network and adhesion complexes during multicellular development of human embryonic stem cells and neuroprogenitor cells. Plexin-B2 manipulations affect actomyosi...
Article
Full-text available
Background This phase I/II trial in patients with recurrent glioblastoma (GBM) evaluates the safety and preliminary efficacy of marizomib, an irreversible pan-proteasome inhibitor that crosses the blood–brain barrier. Patients and Methods Part A assessed the safety and efficacy of marizomib monotherapy. In Part B, escalating doses of marizomib (0....
Article
In neurosurgery, an exact delineation of functional areas is of great interest to spare important regions to ensure the best possible outcome for the patient, i.e. maximum removal while maintaining the highest possible quality of life. Preoperative imaging is routinely performed, including the visualization of not only structural but also functiona...
Article
Glioblastoma (GBM) is an intrinsically treatment-resistant tumor and has been shown to upregulate DNA damage response (DDR) components after treatment. DNA damage response signaling mediates treatment resistance by promoting cell cycle arrest in order to allow for DNA damage repair and avoid mitotic catastrophe. Therefore, targeting the DDR pathway...
Article
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[This corrects the article DOI: 10.1186/s41231-021-00095-0.].
Article
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The WNT (Wingless/Integrated) signaling pathway is implicated in various stages of glioblastoma, which is an aggressive brain tumor for which therapeutic options are limited. WNT has been recognized as a hallmark of therapeutic challenge due to its context-dependent role and critical function in healthy tissue homeostasis. In this review, we deeply...
Article
Full-text available
High‐grade astrocytomas are malignant and aggressive, with limited treatment options. Treatment is geared not only toward increasing patient’s overall survival but also in delaying or preventing neurological disability, a cause of significant morbidity. Increasingly, targeted and customized treatment approaches, especially for recurrent disease, ar...
Article
Full-text available
Brain tumors are among the most lethal tumors. Glioblastoma, the most frequent primary brain tumor in adults, has a median survival time of approximately 15 months after diagnosis or a five-year survival rate of 10%; the recurrence rate is nearly 90%. Unfortunately, this prognosis has not improved for several decades. The lack of progress in the tr...
Article
Full-text available
Background Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entit...
Article
e14033 Background: Advanced age is associated with poorer outcomes in GBM and current NCCN guidelines distinguish older GBM patients (≥70 years, oGBM) from their younger counterparts ( < 70 years, yGBM). We aim to characterize age-related comprehensive mutational profiles with the long-term goal of improving treatment strategies, outcomes, and rati...
Article
Purpose: The current study compared the modified radiographic response assessment in neuro-oncology (mRANO), immunotherapy RANO (iRANO), and standard RANO criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). Experimental design: 47 pati...
Article
Full-text available
The Olig genes encode members of the basic helix-loop-helix (bHLH) family of transcription factors. Olig1, Olig2, and Olig3 are expressed in both the developing and mature central nervous system (CNS) and strictly regulate cellular specification and differentiation. Extensive studies have established functional roles of Olig1 and Olig2 in directing...
Article
Objective: This paper provides a review of current knowledge on intracranial pressure (ICP) dynamics, assessment, and diagnostic considerations, and presents a ladder approach to the management of the neuro-oncological emergency increased ICP. Data source: Review of recent literature from PubMed. Conclusion: Increased ICP can rapidly escalate...