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Prof. Dr. Mustafa Özdoğan · Medical Oncologist

100 Drug Targets for Cancer Immunotherapy Discovered with CRISPR

100 Drug Targets for Cancer Immunotherapy Discovered with CRISPR
In this article

Immunotherapies, among the important developments in cancer treatment in recent years, enable T cells of the immune system to recognize cancer cells and attack them effectively. Immunotherapiesoffer patients with advanced cancers an effective treatment opportunity. However, some patients do not respond successfully. Recently, the different responses seen in patients have prompted investigation of genetic causes. In August 2017, Naturepublished a study in which CRISPR/CAS9 genetic technology discovered 100 immunotherapy drug targets.

The study used the crispr technique to silence each gene and test the response of malignant melanoma skin cancer cells to T cells.

The 2CT CRISPR method developed for this purpose sought to understand each gene's role in skin cancer cells' resistance to immunotherapies.

According to the Research Results;

  • 100 key genes enabling T cells to destroy tumors effectively were identified.
  • The identified candidate geneswere examined together with data from 11.000 tumor samples in the Cancer Genome Project database. A total of 19 genes necessary for T cells' tumor-destroying effects were identified.
  • Researchers focused on the APLNR ( Apelin receptor ) gene. In previous studies, this receptor had been found in different cancer types in a mutated form. This study first described the APLNR gene's role in T cells destroying tumor cells. As a result of 7 mutations in this gene, metastatic melanoma and lung cancer patients do not respond to immune checkpoint inhibitors. In other words, mutations in this gene reduce immunotherapy effectiveness.

What Does This Study Mean for Cancer Treatments?

  • Cancer cells' immunotherapy resistance has a genetic basis that has now largely been clarified.
  • Analyzing these genes before immunotherapy may establish whether a patient will respond to immunotherapy in advance. This allows the most suitable treatment to be selected.
  • The importance of the Crispr technique has once again become clear. Compared with other techniques, Crispr can discover cancer biomarkers or drug targets more quickly.
  • The identified genes' cellular pathways can be examined to develop effective targeted cancer drugs.

You may be interested in: What is the CRISPR/CAS9 genetic technique?

Sources

Shashank J. Patel, Neville E. Sanjana, Rigel J. Kishton ve ark
Identification of essential genes for cancer immunotherapy
Nature, 2017.
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