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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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A second chance for telomerase reverse transcriptase in anticancer immunotherapy.

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Telomerase reverse transcriptase (TERT) is a promising cancer immunotherapy target. Despite modest benefits from past TERT-based vaccines, new insights into TERT genetics and cancer biology offer potential for personalized immunotherapies.

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Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Telomerase reverse transcriptase (TERT) is a tumor-associated antigen targeted for cancer immunotherapy.
  • Previous TERT-based vaccine trials showed limited clinical benefits.
  • TERT is expressed throughout tumor evolution, including in cancer stem cells and metastases.

Purpose of the Study:

  • To explore immunological reasons for limited efficacy of TERT-based immunotherapies.
  • To propose novel strategies for TERT-based immunotherapy development.
  • To highlight the potential of TERT as a target for personalized cancer treatment.

Main Methods:

  • Review of existing literature on TERT in cancer and immunotherapy.
  • Analysis of TERT expression patterns and promoter mutations in various cancers.
  • Discussion of immunological principles relevant to TERT-based therapies.

Main Results:

  • TERT is constitutively expressed in many tumors and plays a role in cancer progression.
  • TERT promoter mutations enhance its transcriptional activation, offering a biomarker.
  • Understanding TERT biology and genetics can inform improved immunotherapy design.

Conclusions:

  • TERT remains a viable target for cancer immunotherapy.
  • Personalized TERT-based immunotherapies, stratified by TERT-promoter mutations, are promising.
  • Combination therapies, potentially with immune-checkpoint inhibitors, may enhance efficacy.