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Challenges to Successful Implementation of the Immune Checkpoint Inhibitors for Treatment of Glioblastoma.

ABSTRACT: Glioblastoma (GBM) is the most common and aggressive malignant glioma, treatment of which has not improved significantly in many years. This is due to the unique challenges that GBM tumors present when designing and implementing therapies. Recently, immunotherapy in the form of immune checkpoint inhibition (ICI) has revolutionized the treatment of various malignancies. The application of immune checkpoint inhibition in GBM treatment has shown promising preclinical results. Unfortunately, this has met with little to no success in the clinic thus far. In this review, we will discuss the challenges presented by GBM tumors that likely limit the effect of ICI and discuss the approaches being tested to overcome these challenges.

SUBMITTER: Sanders S

PROVIDER: S-EPMC7215941 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Challenges to Successful Implementation of the Immune Checkpoint Inhibitors for Treatment of Glioblastoma.

Sanders Stephanie S Debinski Waldemar W

International journal of molecular sciences 20200416 8

Glioblastoma (GBM) is the most common and aggressive malignant glioma, treatment of which has not improved significantly in many years. This is due to the unique challenges that GBM tumors present when designing and implementing therapies. Recently, immunotherapy in the form of immune checkpoint inhibition (ICI) has revolutionized the treatment of various malignancies. The application of immune checkpoint inhibition in GBM treatment has shown promising preclinical results. Unfortunately, this ha ...[more]

PMID: 32316096

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Project description:Hepatocellular carcinoma (HCC) is the most common malignancy worldwide, and is especially common in China. A total of 70%-80% of patients are diagnosed at an advanced stage and can receive only palliative care. Sorafenib has been the standard of care for a decade, and promising results for regorafenib as a second-line and lenvatinib as a first-line treatment were reported only 1 or 2 years ago. FOLFOX4 was recently recommended as a clinical practice guideline by the China Food and Drug Administration. All approved systemic therapies remain unsatisfactory, with limited objective response rates and poor overall survival. Immune checkpoint inhibitors (CPIs) offer great promise in the treatment of a rapidly expanding spectrum of solid tumors. Immune checkpoint molecules are involved in almost the whole process of viral-related hepatitis with cirrhosis and HCC and in the most important resistance mechanism of sorafenib. The approval of nivolumab by the U.S. Food and Drug Administration on September 23, 2017, for the treatment of patients with HCC, based only on a phase I/II clinical trial, is a strong hint that immunotherapy will introduce a new era of HCC therapy. CPI-based strategies will soon be a main approach in anticancer treatment for HCC, and we will observe the rapid advances in the therapeutic use of CPIs, even in an adjuvant setting, with great interest. How shall we face the opportunities and challenges? Can we dramatically improve the prognosis of patients with HCC? This review may provide some informed guidance. IMPLICATIONS FOR PRACTICE: Immune checkpoint molecules are involved in almost the whole process of viral-related hepatitis with cirrhosis and hepatocellular carcinoma (HCC) and in the most important resistance mechanism of sorafenib. As all approved systemic therapies in HCC remain unsatisfactory, checkpoint inhibitor (CPI)-based strategies will soon be a main approach in anticancer treatment for advanced stage of HCC, even in an adjuvant setting. In virus-related HCC, especially hepatitis B virus-related HCC, whether CPIs can control virus relapse should be further investigated. Combination strategies involving conventional therapies and immunotherapies are needed to increase clinical benefit and minimize adverse toxicities with regard to the underlying liver disease.

Dataset Information

Challenges to Successful Implementation of the Immune Checkpoint Inhibitors for Treatment of Glioblastoma.

Publications

Challenges to Successful Implementation of the Immune Checkpoint Inhibitors for Treatment of Glioblastoma.

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