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Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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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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Getting TRAIL back on track for cancer therapy.

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TNF-related apoptosis-inducing ligand (TRAIL) shows promise for selective cancer cell apoptosis. However, limited clinical benefit of TRAIL-receptor agonists (TRAs) is linked to weak activity, cancer cell resistance, and lack of biomarkers. Revised TRAIL-based therapies are proposed.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells.
  • TRAIL-receptor agonists (TRAs) showed preclinical anticancer activity but limited clinical benefit.
  • Factors limiting TRA efficacy include weak agonistic activity, cancer cell resistance, and lack of biomarkers.

Purpose of the Study:

  • To review TRA-based clinical trial outcomes.
  • To discuss shortcomings of current TRA therapies.
  • To propose revised TRAIL-based therapeutic strategies for cancer treatment.

Main Methods:

  • Review of preclinical and clinical studies on TRAIL and TRAs.
  • Analysis of factors contributing to limited clinical efficacy.
  • Integration of insights into TRAIL signaling pathways.

Main Results:

  • TRA clinical trials demonstrated broad tolerability but limited therapeutic benefit.
  • Weak agonistic activity, TRAIL resistance in cancer cells, and absence of biomarkers were identified as key limitations.
  • Recent insights into TRAIL signaling offer potential for improved therapeutic strategies.

Conclusions:

  • Revised TRAIL-based therapeutic concepts are needed to improve clinical outcomes.
  • Strategies include using highly active TRAs, combining TRAs with sensitizing agents, and employing proteomic profiling for biomarker discovery.
  • Personalized TRAIL-based therapies hold promise for future cancer treatment.