scholarly journals Recent Advances in Glioma Therapy: Combining Vascular Normalization and Immune Checkpoint Blockade

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3686
Author(s):  
Rachel L. Y. Ho ◽  
Ivy A. W. Ho
Keyword(s):  
Immune Checkpoint Blockade ◽  
Immune Reactivity ◽  
Vascular Normalization ◽  
Current Standard ◽  
Future Directions ◽  
Pathological Angiogenesis ◽  
Current Standard Treatment ◽  
Cancer Types ◽  
The Brain ◽  
Standard Treatment Regimen

Glioblastoma (GBM) accounts for more than 50% of all primary malignancies of the brain. Current standard treatment regimen for GBM includes maximal surgical resection followed by radiation and adjuvant chemotherapy. However, due to the heterogeneity of the tumor cells, tumor recurrence is often inevitable. The prognosis of patients with glioma is, thus, dismal. Glioma is a highly angiogenic tumor yet immunologically cold. As such, evolving studies have focused on designing strategies that specifically target the tyrosine kinase receptors of angiokines and encourage immune infiltration. Recent promising results from immunotherapies on other cancer types have prompted further investigations of this therapy in GBM. In this article, we reviewed the pathological angiogenesis and immune reactivity in glioma, as well as its target for drug development, and we discussed future directions in glioma therapy.

scholarly journals Suppressing immunotherapy by organ-specific tumor microenvironments: what is in the brain?

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chenyu Zhang ◽  
Dihua Yu
Keyword(s):  
Immune Checkpoint Blockade ◽  
Multiple Cancer ◽  
Tissue Specific ◽  
Tumor Microenvironments ◽  
Specific Tumor ◽  
Organ Specific ◽  
Metastasis Models ◽  
Cancer Types ◽  
The Impact ◽  
The Brain

Abstract Recent breakthroughs in cancer immunotherapy have led to curative efficacy and significantly prolonged survival in a subset of patients of multiple cancer types; and immunotherapy has become the newest pillar of cancer treatment in addition to surgery, chemotherapy, radiotherapy and precision targeted therapies. In the metastatic disease setting, responses to immunotherapy are heterogeneous depending on the metastatic organ sites. The tissue-specific immuno-biology in the tumor microenvironments (TMEs) contributes to the differential therapeutic responses. Herein, we review the impact of tissue-specific tumor microenvironment on the efficacy of immunotherapy, with a focus on historically under-represented central nervous system (CNS) metastasis, which was excluded from most clinical trials. Retrospective examination of patient specimens and prospective clinical studies with immune checkpoint blockade (ICB) have established that brain can harbor an “active” immune microenvironment for effective immunotherapy. Regulation by the innate immune microglial cells and remodeling of the blood–brain barrier (BBB) may contribute to immunotherapeutic responses mediated by T lymphocytes. How to convert an “inactive” (cold) brain microenvironment into an “active” (hot) brain TME should be the focus of future efforts. Thus, procurement and complete examination of clinical specimens from brain metastases as well as development of appropriate preclinical brain metastasis models susceptible to external manipulation of the TME are critical steps towards that goal. A deeper understanding of the immuno-biology in distinct organ microenvironments will help to expand the benefits of immunotherapy to more needed patients.

scholarly journals Introduction to immunotherapy for brain tumor patients: challenges and future perspectives

2020 ◽  
Vol 7 (5) ◽  
pp. 465-476 ◽  
Author(s):  
Megan L Montoya ◽  
Noriyuki Kasahara ◽  
Hideho Okada
Keyword(s):  
Treatment Options ◽  
Malignant Gliomas ◽  
Standard Of Care ◽  
Immune Checkpoint Blockade ◽  
Oncolytic Viruses ◽  
Current Status ◽  
Current Standard ◽  
T Cell Therapy ◽  
Sensitive Organ ◽  
Cancer Types

Abstract Malignant gliomas, including glioblastoma (GBM) as the most aggressive type of adult CNS tumors, are notoriously resistant to current standard of care treatments, including surgery, systemic chemotherapy, and radiation therapy (RT). This lack of effective treatment options highlights the urgent need for novel therapies, including immunotherapies. The overarching goal of immunotherapy is to stimulate and activate the patient’s immune system in a targeted manner to kill tumor cells. The success of immunotherapeutic interventions in other cancer types has led to interest in and evaluation of various experimental immunotherapies in patients with malignant gliomas. However, these primary malignant brain tumors present a challenge because they exist in a vital and sensitive organ with a unique immune environment. The challenges and current status of experimental immunotherapeutic approaches, including vaccines, immune-checkpoint blockade, chimeric antigen receptor T-cell therapy, and oncolytic viruses will be discussed, as well as the potential for combinatorial therapies.

Arsenic trioxide-based nanomedicines as a combination therapeutic approach for treating gliomas: A review

2020 ◽  
Vol 16 ◽  
Author(s):  
Rabeea Siddique ◽  
Suliman Khan ◽  
Qian Bai ◽  
Hongmin Li ◽  
Muhammad Wajid Ullah ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Standard Treatment ◽  
High Dose ◽  
Pharmacological Treatments ◽  
Current Standard ◽  
Therapeutic Drugs ◽  
Large Size ◽  
Penetration Ability ◽  
Current Standard Treatment ◽  
The Brain

: Glioblastoma is one of the fatal and aggressive types of brain tumors. The current standard treatment for glioblastoma multiform (GBM) is surgical resection coupled with radiotherapy and chemotherapy. Although ample research has been performed, and multiple novel pharmacological approaches have been investigated for developing effective therapeutic drugs for treating GBM, the success of extending the survival of the patient is notably low. The unique barrier limiting GBM treatment is the presence of the blood-brain barrier (BBB), and most of the chemotherapeutic drugs fail to cross it due to their high molecular weight and large size. The currently used chemo drugs for GBM have poor penetration ability to the brain and cause off-target toxicity due to a high dose for maintaining drug concentration at the tumor site. The use of nanomaterial composites for co-delivery of multiple therapeutic drugs offers several advantages by encompassing the aforementioned obstacles. In this review, the first part sheds light on the characteristics of GBM and the major challenges faced by the current pharmacological treatments. The second part emphasizes the application of nanomaterials-based nanotherapeutics to overcome the challenges associated with current GBM therapy. A closer look is given to the use of FDA approved traditional Chinese medicine arsenic trioxide (ATO) and its application as co-delivery nanoparticles (i.e., ATO-NPs) against solid tumors, especially gliomas. In short, a breakthrough in nanotechnology offers a promising platform to treat GBM; however, rigorous efforts need to be devoted in order to develop novel therapeutic drugs with higher therapeutic efficiency and limited side effects.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Adding perphenazine to increase effectiveness of standard glioblastoma chemoirradiation. (Preprint)

2020 ◽  
Author(s):  
Richard Kast
Keyword(s):  
Dopamine Receptor ◽  
Subventricular Zone ◽  
Serotonin Receptor ◽  
Treatment Effectiveness ◽  
Short Note ◽  
Recurrent Glioblastoma ◽  
Current Standard ◽  
Medically Ill ◽  
Current Standard Treatment ◽  
Protein Phosphatase 2

UNSTRUCTURED In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular reference to intersections with the pharmacology of perphenazine. That study identified five areas of potentially beneficial intersection. Data showed seemingly 5 independent perphenazine attributes of benefit to glioblastoma treatment - i) blocking dopamine receptor 2, ii) reducing centrifugal migration of subventricular zone cells by blocking dopamine receptor 3, iii) blocking serotonin receptor 7, iv) activation of protein phosphatase 2, and v) nausea reduction. Perphenazine is fully compatible with current chemoirradiation protocols and with the commonly used ancillary medicines used in clinical practice during the course of glioblastoma. All these attributes argue for a trial of perphenazine’s addition to current standard treatment with temozolomide and irradiation. The subventricular zone seeds the brain with mutated cells that become recurrent glioblastoma after centrifugal migration. The current paper shows how perphenazine might reduce that contribution. Perphenazine is an old, generic, cheap, phenothiazine antipsychotic drug that has been in continuous clinical use worldwide since the 1950’s. Clinical experience and research data over these decades have shown perphenazine to be well-tolerated in psychiatric populations, in normals, and in non-psychiatric, medically ill populations for whom perphenazine is used to reduce nausea. For now (Summer, 2020) the nature of glioblastoma requires a polypharmacy approach until/unless a core feature and means to address it can be identified in the future. Conclusions: Perphenazine possesses a remarkable constellation of attributes that recommend its use in GB treatment.

Alcohol Use Disorder

2018 ◽  
Author(s):  
Igor Ponomarev
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Critical Discussion ◽  
Epigenetic Mechanisms ◽  
Future Directions ◽  
Clinically Significant ◽  
Early Life Exposures ◽  
The Brain ◽  
Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

scholarly journals Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

2021 ◽  
Author(s):  
Haoru Dong ◽  
Xinhua Shu ◽  
Qiang Xu ◽  
Chen Zhu ◽  
Andreas M. Kaufmann ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Treatment Strategies ◽  
Hpv Infection ◽  
Immune Checkpoint Blockade ◽  
Current Status ◽  
Future Directions ◽  
Sequencing Technologies ◽  
E6 And E7 ◽  
The Continuum

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.

scholarly journals TEM8/ANTXR1 Blockade Inhibits Pathological Angiogenesis and Potentiates Tumoricidal Responses against Multiple Cancer Types

Cancer Cell ◽  
2012 ◽  
Vol 21 (2) ◽  
pp. 212-226 ◽  
Author(s):  
Amit Chaudhary ◽  
Mary Beth Hilton ◽  
Steven Seaman ◽  
Diana C. Haines ◽  
Susan Stevenson ◽  
...  
Keyword(s):  
Multiple Cancer ◽  
Pathological Angiogenesis ◽  
Cancer Types

EXTH-56. ZIKA VIRUS TREATMENT SIGNIFICANTLY PROLONGS SURVIVAL IN A GLIOBLASTOMA PATIENT DERIVED XENOGRAFT MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi175-vi176
Author(s):  
Parvez Akhtar ◽  
Samuel Zwernik ◽  
Deborah Donohoe ◽  
Catherine Warner ◽  
Dmitry Bosenko ◽  
...  
Keyword(s):  
Median Survival ◽  
Zika Virus ◽  
Oncolytic Virus ◽  
Xenograft Model ◽  
Standard Of Care ◽  
Control Group ◽  
Current Standard ◽  
Patient Derived Xenograft ◽  
Current Standard Treatment ◽  
Tumor Remission

Abstract The poor median survival for patients with glioblastoma (GBM) of 15 months has not budged for the past 15 years, when the current standard treatment was first approved. There is no standard of care chemotherapy for recurrent GBM. We previously showed that Zika virus (ZIKV) tropism for GBM cells is mediated through the receptor tyrosine kinase, AXL. This infection is cytotoxic. In this study we show that ZIKV is an effective oncolytic virus in a patient derived xenograft model. Fox N1 Nude homozygous female mice 6-8-weeks-old were grouped into 4 experimental arms: two patient derived cell lines, each with a ZIKV treated and a control group. There were 12 mice in each arm. Animals received subcutaneous flank injections of GBM 8049 or its AXL CRISPR knockout 8049 AXLKO (2x106 cells). When tumors reached 200 mm3, mice received intra-tumoral injection of 2.5x106 ZIKV particles or saline. ZIKV induced complete tumor remission in 22 of 24 animals (8049: 11/12; 8049 AXLKO: 11/12). There was no tumor remission in the saline treated animals. Median survival of 8049 and 8049 AXLKO ZIKV treated mice was 124 days and 125 days, respectively. This is compared to median survival of control animals 8049: 42 days; 8049 AXLKO: 46 days (P= 0.001). Among ZIKV treated mice, there were two recurrences: one in the 8049 tumor (24 days after significant tumor remission) and one 8049 AXLKO tumor (7 days after significant tumor remission). We conclude that ZIKV should be considered a candidate oncolytic virus for GBM.

Sign in / Sign up

Export Citation Format

Share Document