Immunotherapy in glioblastoma: emerging options in precision medicine.
Ontology highlight
ABSTRACT:
SUBMITTER: Hodges TR
PROVIDER: S-EPMC4926530 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Immunotherapy in glioblastoma: emerging options in precision medicine.
Hodges Tiffany R TR Ferguson Sherise D SD Heimberger Amy B AB
CNS oncology 20160526 3
Immunotherapy for glioblastoma (GBM) provides a unique opportunity for targeted therapies for each patient, addressing individual variability in genes, tumor biomarkers and clinical profile. As immunotherapy has the potential to specifically target tumor cells with minimal risk to normal tissue, several immunotherapeutic strategies are currently being evaluated in clinical trials in GBM. With the Precision Medicine Initiative being announced in the President's State of the Union Address in 2016, ...[more]
Similar Datasets
Project description:Brain metastases (BM) continue to represent an unmet clinical need in oncology. Immunotherapy and targeted therapy hold great promise in the treatment of BM. Emerging data are confirming the activity of these agents in patients with BM. Genomic studies have confirmed that clinically actionable mutations are present in BM and they can be used in clinical studies to link targeted therapies with their genetic targets. Furthermore, as molecular signatures associated with sensitivity and resistance to immunotherapies are developed, we will better be able to select BM patients who will most benefit from these therapies. Understanding the genetic and immune evolution within BM should drive the next generation of immunotherapy and target therapy, as well as increase the accuracy of the selection process for these therapies.
| S-EPMC6020878 | biostudies-other
Project description:Owing to the advancement of technology combined with our deeper knowledge of human nature and diseases, we are able to move towards precision medicine, where patients are treated at the individual level in concordance with their genetic profiles. Lately, the integration of nanoparticles in biotechnology and their applications in medicine has allowed us to diagnose and treat disease better and more precisely. As a model disease, we used a grade IV malignant brain tumor (glioblastoma). Significant improvements in diagnosis were achieved with the application of fluorescent nanoparticles for intraoperative magnetic resonance imaging (MRI), allowing for improved tumor cell visibility and increasing the extent of the surgical resection, leading to better patient response. Fluorescent probes can be engineered to be activated through different molecular pathways, which will open the path to individualized glioblastoma diagnosis, monitoring, and treatment. Nanoparticles are also extensively studied as nanovehicles for targeted delivery and more controlled medication release, and some nanomedicines are already in early phases of clinical trials. Moreover, sampling biological fluids will give new insights into glioblastoma pathogenesis due to the presence of extracellular vesicles, circulating tumor cells, and circulating tumor DNA. As current glioblastoma therapy does not provide good quality of life for patients, other approaches such as immunotherapy are explored. To conclude, we reason that development of personalized therapies based on a patient's genetic signature combined with pharmacogenomics and immunogenomic information will significantly change the outcome of glioblastoma patients.
| S-EPMC7038132 | biostudies-literature
Project description:Immunotherapy has shown clinical benefits in several solid malignancies-in particular, melanoma and non-small cell lung cancer. However, in other solid tumours such as glioblastoma (GBM), the response to immunotherapy has been more variable, and except for anti-PD-1 for patients with microsatellite instable (MSI)+ cancers, no immunotherapy is currently approved for GBM patients. GBM is the most common and most aggressive brain cancer with a very poor prognosis and a median overall survival of 15 months. A few prognostic biomarkers have been identified and are used to some extent, but apart from MSI, no biomarkers are used for patient stratification for treatments other than the standard of care, which was established 15 years ago. Around 25% of new treatments investigated in GBM are immunotherapies. Recent studies indicate that the use of integrated and validated immune correlates predicting the response and guiding treatments could improve the efficacy of immunotherapy in GBM. In this review, we will give an overview of the current status of immunotherapy and biomarkers in use in GBM with the main challenges of treatment in this disease. We will also discuss emerging biomarkers that could be used in future immunotherapy strategies for patient stratification and potentially improved treatment efficacy.
| S-EPMC9024739 | biostudies-literature
Project description:Precision medicine is an integrative approach to cardiovascular disease prevention and treatment that considers an individual's genetics, lifestyle, and exposures as determinants of their cardiovascular health and disease phenotypes. This focus overcomes the limitations of reductionism in medicine, which presumes that all patients with the same signs of disease share a common pathophenotype and, therefore, should be treated similarly. Precision medicine incorporates standard clinical and health record data with advanced panomics (ie, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics) for deep phenotyping. These phenotypic data can then be analyzed within the framework of molecular interaction (interactome) networks to uncover previously unrecognized disease phenotypes and relationships between diseases, and to select pharmacotherapeutics or identify potential protein-drug or drug-drug interactions. In this review, we discuss the current spectrum of cardiovascular health and disease, population averages and the response of extreme phenotypes to interventions, and population-based versus high-risk treatment strategies as a pretext to understanding a precision medicine approach to cardiovascular disease prevention and therapeutic interventions. We also consider the search for resilience and Mendelian disease genes and argue against the theory of a single causal gene/gene product as a mediator of the cardiovascular disease phenotype, as well as an Erlichian magic bullet to solve cardiovascular disease. Finally, we detail the importance of deep phenotyping and interactome networks and the use of this information for rational polypharmacy. These topics highlight the urgent need for precise phenotyping to advance precision medicine as a strategy to improve cardiovascular health and prevent disease.
| S-EPMC6021027 | biostudies-literature
Project description:Biliary tracts cancers (BTCs) are a diverse group of aggressive malignancies with an overall poor prognosis. Genomic characterization has uncovered many putative clinically actionable aberrations that can also facilitate the prognostication of patients. As such, comprehensive genomic profiling is playing a growing role in the clinical management of BTCs. Currently however, there is only one precision medicine approved by the US Food and Drug Administration (FDA) for the treatment of BTCs. Herein, we highlight the prevalence and prognostic, diagnostic, and predictive significance of recurrent mutations and other genomic aberrations with current clinical implications or emerging relevance to clinical practice. Some ongoing clinical trials, as well as future areas of exploration for precision oncology in BTCs are highlighted.
| S-EPMC6170410 | biostudies-literature
Project description:Over the past decade, the treatment landscape of CLL has vastly changed from the conventional FC (fludarabine and cyclophosphamide) and FCR (FC with rituximab) chemotherapies to targeted therapies, including inhibitors of Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) as well as inhibitors of BCL2. These treatment options dramatically improved clinical outcomes; however, not all patients respond well to these therapies, especially high-risk patients. Clinical trials of immune checkpoint inhibitors (PD-1, CTLA4) and chimeric antigen receptor T (CAR T) or NK (CAR NK) cell treatment have shown some efficacy; still, long-term outcomes and safety issues have yet to be determined. CLL remains an incurable disease. Thus, there are unmet needs to discover new molecular pathways with targeted or combination therapies to cure the disease. Large-scale genome-wide whole-exome and whole-genome sequencing studies have discovered genetic alterations associated with disease progression, refined the prognostic markers in CLL, identified mutations underlying drug resistance, and pointed out critical targets to treat the disease. More recently, transcriptome and proteome landscape characterization further stratified the disease and revealed novel therapeutic targets in CLL. In this review, we briefly summarize the past and present available single or combination therapies, focusing on potential emerging therapies to address the unmet clinical needs in CLL.
| S-EPMC10000606 | biostudies-literature
Project description:Prostate cancer (PCa) has been known as the most prevalent cancer disease and the second leading cause of cancer mortality in men almost all over the globe. There is an urgent need for establishment of PCa models that can recapitulate the progress of genomic landscapes and molecular alterations during development and progression of this disease. Notably, several organoid models have been developed for assessing the complex interaction between PCa and its surrounding microenvironment. In recent years, PCa organoids have been emerged as powerful in vitro 3D model systems that recapitulate the molecular features (such as genomic/epigenomic changes and tumor microenvironment) of PCa metastatic tumors. In addition, application of organoid technology in mechanistic studies (i.e., for understanding cellular/subcellular and molecular alterations) and translational medicine has been recognized as a promising approach for facilitating the development of potential biomarkers and novel therapeutic strategies. In this review, we summarize the application of PCa organoids in the high-throughput screening and establishment of relevant xenografts for developing novel therapeutics for metastatic, castration resistant, and neuroendocrine PCa. These organoid-based studies are expected to expand our knowledge from basic research to clinical applications for PCa diseases. Furthermore, we also highlight the optimization of PCa cultures and establishment of promising 3D organoid models for in vitro and in vivo investigations, ultimately facilitating mechanistic studies and development of novel clinical diagnosis/prognosis and therapies for PCa.
| S-EPMC10816550 | biostudies-literature
Project description:Integrated sequencing strategies have provided a broader understanding of the genomic landscape and molecular classifications of multiple cancer types and have identified various therapeutic opportunities across cancer subsets. Despite pivotal advances in the characterization of genomic alterations in glioblastoma, targeted agents have shown minimal efficacy in clinical trials to date, and patient survival remains poor. In this review, we highlight potential reasons why targeting single alterations has yielded limited clinical efficacy in glioblastoma, focusing on issues of tumor heterogeneity and pharmacokinetic failure. We outline strategies to address these challenges in applying precision medicine to glioblastoma and the rationale for applying targeted combination therapy approaches that match genomic alterations with compounds accessible to the central nervous system.
| S-EPMC4490873 | biostudies-literature
Project description:Simple Summary There are some challenges to improve the clinical outcome of colorectal cancers (CRCs) by implementing new technologies, such as early detection of recurrence/relapse and selection of appropriate drugs based on the genomic profiles of tumors. For example, the genomic characteristics of tumors can be analyzed by blood-based tests, namely ‘liquid biopsies’, which are minimally-invasive and can be performed repeatedly during the treatment course. Hence, liquid biopsies are considered to hold great promise to fill these gaps in clinical routines. In this review, we addressed clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of minimal residual disease, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. Furthermore, we discussed the possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information. Abstract In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades. However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive. We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients. With the recent technological advances in methodologies and bioinformatics, the genomic profiles can be analyzed profoundly without delay by blood-based tests—‘liquid biopsies’. From a clinical point of view, a minimally-invasive liquid biopsy is thought to be a promising method and can be implemented in routine clinical settings in order to meet unmet clinical needs. In this review, we highlighted clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of MRD, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. In addition, we addressed a possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information.
| S-EPMC8507967 | biostudies-literature
Project description:In recent years, numerous clinical trials for disease modification in Parkinson's disease (PD) have failed, possibly because of a "one-size-fits all" approach. Alternatively, a precision medicine approach, which customises treatments based on patients' individual genotype, may help reach disease modification. Here, we review clinical trials that target genetic forms of PD, i.e., GBA-associated and LRRK2-associated PD. In summary, six ongoing studies which explicitely recruit GBA-PD patients, and two studies which recruit LRRK2-PD patients, were identified. Available data on mechanisms of action, study design, and challenges of therapeutic trials are discussed.
| S-EPMC7035220 | biostudies-literature