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Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications

Johann S. Bergholz, Qiwei Wang, Sheheryar Kabraji and Jean J. Zhao
Johann S. Bergholz
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
3Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
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  • For correspondence: jean_zhao@dfci.harvard.edu johann_bergholz@dfci.harvard.edu
Qiwei Wang
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
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Sheheryar Kabraji
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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Jean J. Zhao
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
3Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
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  • For correspondence: jean_zhao@dfci.harvard.edu johann_bergholz@dfci.harvard.edu
DOI: 10.1158/1078-0432.CCR-19-2300 Published November 2020
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Abstract

Small-molecule targeted therapies have demonstrated outstanding potential in the clinic. These drugs are designed to minimize adverse effects by selectively attacking cancer cells while exerting minimal damage to normal cells. Although initial response to targeted therapies may be high, yielding positive response rates and often improving survival for an important percentage of patients, resistance often limits long-term effectiveness. On the other hand, immunotherapy has demonstrated durable results, yet for a limited number of patients. Growing evidence indicates that some targeted agents can modulate different components of the antitumor immune response. These include immune sensitization by inhibiting tumor cell–intrinsic immune evasion programs or enhancing antigenicity, as well as direct effects on immune effector and immunosuppressive cells. The combination of these two approaches, therefore, has the potential to result in synergistic and durable outcomes for patients. In this review, we focus on the latest advances on integrating immunotherapy with small-molecule targeted inhibitors. In particular, we discuss how specific oncogenic events differentially affect immune response, and the implications of these findings on the rational design of effective combinations of immunotherapy and targeted therapies.

Footnotes

  • Clin Cancer Res 2020;26:5557–66

  • Received January 15, 2020.
  • Revision received May 8, 2020.
  • Accepted June 19, 2020.
  • Published first June 23, 2020.
  • ©2020 American Association for Cancer Research.
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Clinical Cancer Research: 26 (21)
November 2020
Volume 26, Issue 21
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Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications
Johann S. Bergholz, Qiwei Wang, Sheheryar Kabraji and Jean J. Zhao
Clin Cancer Res November 1 2020 (26) (21) 5557-5566; DOI: 10.1158/1078-0432.CCR-19-2300

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Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications
Johann S. Bergholz, Qiwei Wang, Sheheryar Kabraji and Jean J. Zhao
Clin Cancer Res November 1 2020 (26) (21) 5557-5566; DOI: 10.1158/1078-0432.CCR-19-2300
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  • Article
    • Abstract
    • Introduction
    • Immune Evasion by Cancer Cells
    • Oncogenic Signaling Pathways Shape the Tumor Immune Microenvironment
    • Integrating Small-molecule Targeted Therapy and Immunotherapy to Improve Therapeutic Outcomes
    • Future Prospects
    • Disclosure of Potential Conflicts of Interest
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Clinical Cancer Research
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