scholarly journals Immunotherapy for Glioblastoma: Current Progress and Challenge

2021 ◽  
Vol 12 ◽  
Author(s):  
Miranda W. Yu ◽  
Daniela F. Quail
Keyword(s):  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Sufficient Evidence ◽  
Small Cell Lung ◽  
Current Standard ◽  
Recent Success ◽  
Tumor Plasticity ◽  
Additional Challenge ◽  
The Central Nervous System ◽  
Median Survival Rate

Glioblastoma is a highly lethal brain cancer with a median survival rate of less than 15 months when treated with the current standard of care, which consists of surgery, radiotherapy and chemotherapy. With the recent success of immunotherapy in other aggressive cancers such as advanced melanoma and advanced non-small cell lung cancer, glioblastoma has been brought to the forefront of immunotherapy research. Resistance to therapy has been a major challenge across a multitude of experimental candidates and no immunotherapies have been approved for glioblastoma to-date. Intra- and inter-tumoral heterogeneity, an inherently immunosuppressive environment and tumor plasticity remain barriers to be overcome. Moreover, the unique tissue-specific interactions between the central nervous system and the peripheral immune system present an additional challenge for immune-based therapies. Nevertheless, there is sufficient evidence that these challenges may be overcome, and immunotherapy continues to be actively pursued in glioblastoma. Herein, we review the primary ongoing immunotherapy candidates for glioblastoma with a focus on immune checkpoint inhibitors, myeloid-targeted therapies, vaccines and chimeric antigen receptor (CAR) immunotherapies. We further provide insight on mechanisms of resistance and how our understanding of these mechanisms may pave the way for more effective immunotherapeutics against glioblastoma.

scholarly journals Glioblastoma Multiforme—A Look at the Past and a Glance at the Future

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1053
Author(s):  
Jasmine L. King ◽  
Soumya Rahima Benhabbour
Keyword(s):  
Glioblastoma Multiforme ◽  
Immune Surveillance ◽  
Standard Of Care ◽  
Current Standard ◽  
Comprehensive Overview ◽  
Therapeutic Delivery ◽  
The Past ◽  
Adults And Children ◽  
The Central Nervous System ◽  
Delivery Strategies

Gliomas are the most common type of brain tumor that occur in adults and children. Glioblastoma multiforme (GBM) is the most common, aggressive form of brain cancer in adults and is universally fatal. The current standard-of-care options for GBM include surgical resection, radiotherapy, and concomitant and/or adjuvant chemotherapy. One of the major challenges that impedes success of chemotherapy is the presence of the blood–brain barrier (BBB). Because of the tightly regulated BBB, immune surveillance in the central nervous system (CNS) is poor, contributing to unregulated glioma cell growth. This review gives a comprehensive overview of the latest advances in treatment of GBM with emphasis on the significant advances in immunotherapy and novel therapeutic delivery strategies to enhance treatment for GBM.

scholarly journals Front Line Applications and Future Directions of Immunotherapy in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 506
Author(s):  
Selina K. Wong ◽  
Wade T. Iams
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Limited Stage ◽  
Extensive Stage

After being stagnant for decades, there has finally been a paradigm shift in the treatment of small-cell lung cancer (SCLC) with the emergence and application of immune checkpoint inhibitors (ICIs). Multiple trials of first-line ICI-chemotherapy combinations have demonstrated survival benefit compared to chemotherapy alone in patients with extensive-stage SCLC, establishing this as the new standard of care. ICIs are now being applied in the potentially curative limited-stage setting, actively being investigated as concurrent treatment with chemoradiation and as adjuvant treatment following completion of chemoradiation. This review highlights the evidence behind the practice-changing addition of ICIs in the first-line setting of extensive-stage SCLC, the potentially practice-changing immunotherapy trials that are currently underway in the limited-stage setting, and alternate immunotherapeutic strategies being studied in the treatment of SCLC.

scholarly journals Small Cell Lung Cancer from Traditional to Innovative Therapeutics: Building a Comprehensive Network to Optimize Clinical and Translational Research

2020 ◽  
Vol 9 (8) ◽  
pp. 2433 ◽  
Author(s):  
Shanmuga Subbiah ◽  
Arin Nam ◽  
Natasha Garg ◽  
Amita Behal ◽  
Prakash Kulkarni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Complex Disease ◽  
Standard Of Care ◽  
Small Cell ◽  
Community Practice ◽  
Small Cell Lung ◽  
Current Standard ◽  
Drug Target Discovery

Small cell lung cancer (SCLC) is an aggressive, complex disease with a distinct biology that contributes to its poor prognosis. Management of SCLC is still widely limited to chemotherapy and radiation therapy, and research recruitment still poses a considerable challenge. Here, we review the current standard of care for SCLC and advances made in utilizing immunotherapy. We also highlight research in the development of targeted therapies and emphasize the importance of a team-based approach to make clinical advances. Building an integrative network between an academic site and community practice sites optimizes biomarker and drug target discovery for managing and treating a difficult disease like SCLC.

New Directions in the Treatment of Glioblastoma

2018 ◽  
Vol 38 (01) ◽  
pp. 050-061 ◽  
Author(s):  
Zachary Reitman ◽  
Frank Winkler ◽  
Andrew Elia
Keyword(s):  
Standard Of Care ◽  
Multimodality Treatment ◽  
Genetic Alterations ◽  
Current Standard ◽  
The Past ◽  
Molecular Features ◽  
Genome Wide ◽  
New Directions ◽  
The Central Nervous System ◽  
Better Than

Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis. Here, we review these molecular features and discuss major clinical trials that have recently defined the field. We describe genetic alterations in isocitrate dehydrogenase, ATRX, the telomerase promoter, and histone H3 variants that promote GBM tumorigenesis and have altered GBM categorization. We also discuss intratumoral genetic heterogeneity as one explanation for therapeutic failures and explain how ultra-long extensions of glioma cells, called tumor microtubes, mediate therapeutic resistance. These findings provide new insights into GBM biology and offer hope for the development of next-generation therapies.

scholarly journals Immunotherapy Strategies for Gastrointestinal Stromal Tumor

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3525
Author(s):  
Junaid Arshad ◽  
Philippos A. Costa ◽  
Priscila Barreto-Coelho ◽  
Brianna Nicole Valdes ◽  
Jonathan C. Trent
Keyword(s):  
Monoclonal Antibodies ◽  
Soft Tissue ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Standard Of Care ◽  
Current Standard ◽  
Molecular Alterations

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST.

scholarly journals Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies

2021 ◽  
Vol 22 (7) ◽  
pp. 3493
Author(s):  
Vassilis Genoud ◽  
Denis Migliorini
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Standard Of Care ◽  
Current Standard ◽  
Future Directions ◽  
Broad Application ◽  
The Road ◽  
The Central Nervous System ◽  
Primary Neoplasm ◽  
Made In

Glioblastoma is the most frequent primary neoplasm of the central nervous system and still suffers from very poor therapeutic impact. No clear improvements over current standard of care have been made in the last decade. For other cancers, but also for brain metastasis, which harbors a very distinct biology from glioblastoma, immunotherapy has already proven its efficacy. Efforts have been pursued to allow glioblastoma patients to benefit from these new approaches, but the road is still long for broad application. Here, we aim to review key glioblastoma immune related characteristics, current immunotherapeutic strategies being explored, their potential caveats, and future directions.

scholarly journals Checkpoint Inhibitors as High-Grade Gliomas Treatment: State of the Art and Future Perspectives

2021 ◽  
Vol 10 (7) ◽  
pp. 1367
Author(s):  
Pasquale Persico ◽  
Elena Lorenzi ◽  
Angelo Dipasquale ◽  
Federico Pessina ◽  
Pierina Navarria ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
State Of The Art ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Immune Checkpoint Blockade ◽  
High Grade ◽  
Current Standard ◽  
Advanced Malignancies ◽  
The Status ◽  
High Grade Gliomas

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Despite significant efforts, no therapies have demonstrated valuable survival benefit beyond the current standard of care. Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape and improved patient survival in many advanced malignancies. Unfortunately, these clinical successes have not been replicated in the neuro-oncology field so far. This review summarizes the status of ICI investigation in high-grade gliomas, critically presenting the available data from preclinical models and clinical trials. Moreover, we explore new approaches to increase ICI efficacy, with a particular focus on combinatorial strategies, and the potential biomarkers to identify patients most likely to benefit from immune checkpoint blockade.

scholarly journals The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with a hypermutant, hypermethylated state

2020 ◽  
Author(s):  
Sally Hallam ◽  
Joanne Stockton ◽  
Claire Bryer ◽  
Celina Whalley ◽  
Valerie Pestinger ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Patient Selection ◽  
Poor Prognosis ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Negative Regulator ◽  
Current Standard ◽  
Molecular Features ◽  
Heated Intraperitoneal Chemotherapy

ABSTRACTColoretcal Peritoneal metastases (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) is the current standard of care in selected patients with limited resectable CPM. Despite selection using known prognostic factors survival is varied and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning the biology of isolated CPM. We aimed to determine the biology associated with transition from primary CRC to CPM and poor prognosis CPM, to identify those suitable for treatment with CRS & HIPEC and to identify targets for existing repurposed or novel treatment strategies. A cohort of patients with CPM treated with CRS & HIPEC was recruited and divided according to prognosis. Molecular profiling of the transcriptome, epigenome and genome of CPM and matched primary CRC was performed.CPM were characterised by frequent Wnt/ β catenin negative regulator mutations, mismatch repair mutations and resulting high tumour mutational burden and dysregulation of methylation suggested by frequent TET2 mutations and mutations suggesting an immune evasive phenotype. Several novel therapies could be targeted to these frequent mutations including porcupine inhibitors, immune checkpoint inhibitors and methylation inhibitors. Here we show the molecular features associated with CPM development and with poor prognosis. Potential applications include improving patient selection for treatment and in the development of novel and personalised treatments.NOVELTY AND IMPACTColorectal peritoneal metastasis (CPM) are associated with limited and variable survival despite patient selection using known prognostic factors and optimal currently available treatments. There is a paucity of research concerning the biology of CPM. This study describes the biological landscape of CPM and the molecular features associated with CPM development, conferring poor prognosis and has identified that the majority of CPM develop a hypermutant phenotype that may be suitable for treatment with anti-PD1/CTLA4 immunotherapy.

scholarly journals Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR

2021 ◽  
Vol 11 ◽  
Author(s):  
Karan Seegobin ◽  
Umair Majeed ◽  
Nathaniel Wiest ◽  
Rami Manochakian ◽  
Yanyan Lou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Standard Of Care ◽  
Small Cell ◽  
Published Data ◽  
Small Cell Lung ◽  
Current Standard ◽  
Lung Cancers

While first line targeted therapies are the current standard of care treatment for non-small cell lung cancer (NSCLC) with actionable mutations, the cancer cells inevitably acquire resistance to these agents over time. Immune check-point inhibitors (ICIs) have improved the outcomes of metastatic NSCLC, however, its efficacy in those with targetable drivers is largely unknown. In this manuscript, we reviewed the published data on ICI therapies in NSCLC with ALK, ROS1, BRAF, c-MET, RET, NTRK, KRAS, and HER2 (ERBB2) alterations. We found that the objective response rates (ORRs) associated with ICI treatments in lung cancers harboring the BRAF (0–54%), c-MET (12–49%), and KRAS (18.7-66.7%) alterations were comparable to non-mutant NSCLC, whereas the ORRs in RET fusion NSCLC (less than10% in all studies but one) and ALK fusion NSCLC (0%) were relatively low. The ORRs reported in small numbers of patients and studies of ROS1 fusion, NTRK fusion, and HER 2 mutant NSCLC were 0–17%, 50% and 7–23%, respectively, making the efficacy of ICIs in these groups of patients less clear. In most studies, no significant correlation between treatment outcome and PD-L1 expression or tumor mutation burden (TMB) was identified, and how to select patients with NSCLC harboring actionable mutations who will likely benefit from ICI treatment remains unknown.

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