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Prof. Dr. Mustafa Özdoğan · Medical Oncologist

CRISPR-Cas9 Technology Identifies a New Immunotherapy Target in Cancer

CRISPR-Cas9 Technology Identifies a New Immunotherapy Target in Cancer
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One of the most important discoveries of the 21st century, CRISPR/CAS9 genetic technology, not only offers effective treatments against cancer but also supports research into biomarkers and drug targets in cancer. Research undertaken for this purpose discovered that the protein called TPN2determines the effectiveness of immune checkpoint inhibitors, the new generation of immunotherapies.

Immune checkpoint inhibitor immunotherapiesare cancer treatments introduced after 2011 that activate the immune system to attack cancer rather than directly killing cancer cells.

In July 2017, Naturepublished a notable study in which thousands of tumor genes were added and removed using CRISPR to examine their functions in the laboratory. In a study in mice, researchers systematically silenced genes in cells of the skin cancer melanoma , using CRISPR to silence 2.368 genes and investigate which genes reduced the effectiveness of immunotherapy drugs.

According to the Study Findings:

  • Blocking the activity of the PTPN2 (protein tyrosine phosphatase) gene increased the effects of immunotherapy drugs.
  • PTPN2 enables cancer cells to develop resistance to immunotherapies.
  • PTPN2 is a protein that plays an active role in cell growth pathways . It functions in pathways involved in cell growth, differentiation, and the transformation of cells into cancer cells.

What Does This Study Mean Clinically?

  • CRISPR can rapidly screen genes and identify their functions, enabling the discovery of new drug targets.
  • Another reason why immunotherapy does not benefit some patients has been identified. Targeting PTPN2 could improve immunotherapy effectiveness.
  • Developing new-generation PTPN2 inhibitors could offer more effective cancer treatment.
  • This newly developed technique could rapidly screen the entire genome in other cancer types and identify the reasons for differences in treatment responses.

Sources

Robert T. Manguso, Hans W. Pope, Margaret D. Zimmer et. al.
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.
Nature, July 2017
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