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Sharma et al. Cancer Drug Resist 2023;6:688-708 Cancer
DOI: 10.20517/cdr.2023.82
Drug Resistance

Review Open Access

Drug resistance in glioblastoma: from chemo- to

immunotherapy

Sachin Sharma, Oksana Chepurna, Tao Sun
Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Correspondence to: Dr. Tao Sun, Department of Neurosurgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles,
CA 90048, USA. E-mail: tao.sun@cshs.org

How to cite this article: Sharma S, Chepurna O, Sun T. Drug resistance in glioblastoma: from chemo- to immunotherapy. Cancer
Drug Resist 2023;6:688-708. https://dx.doi.org/10.20517/cdr.2023.82

Received: 17 Jul 2023 First Decision: 1 Sep 2023 Revised: 7 Sep 2023 Accepted: 25 Sep 2023 Published: 11 Oct 2023

Academic Editor: Godefridus J. Peters Copy Editor: Pei-Yun Wang Production Editor: Pei-Yun Wang

Abstract
As the most common and aggressive type of primary brain tumor in adults, glioblastoma is estimated to end over
10,000 lives each year in the United States alone. Stand treatment for glioblastoma, including surgery followed by
radiotherapy and chemotherapy (i.e., Temozolomide), has been largely unchanged since early 2000. Cancer
immunotherapy has significantly shifted the paradigm of cancer management in the past decade with various
degrees of success in treating many hematopoietic cancers and some solid tumors, such as melanoma and non-
small cell lung cancer (NSCLC). However, little progress has been made in the field of neuro-oncology, especially in
the application of immunotherapy to glioblastoma treatment. In this review, we attempted to summarize the
common drug resistance mechanisms in glioblastoma from Temozolomide to immunotherapy. Our intent is not to
repeat the well-known difficulty in the area of neuro-oncology, such as the blood-brain barrier, but to provide some
fresh insights into the molecular mechanisms responsible for resistance by summarizing some of the most recent
literature. Through this review, we also hope to share some new ideas for improving the immunotherapy outcome
of glioblastoma treatment.

Keywords: Glioblastoma, immunotherapy, drug resistance, tumor microenvironment, immunosuppression

INTRODUCTION
Brain tumors affect more than ~17,000 people in the United States each year, where gliomas are considered

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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