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Emerging targeted therapies and strategies to overcome resistance in biliary tract cancers

Tarik Demir1, Carolyn Moloney1, Devalingam Mahalingam1

  • 1Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine1, Chicago, IL 60611, USA.

Critical Reviews in Oncology/Hematology
|May 16, 2024
PubMed

Insights

Targeted therapies and immune checkpoint inhibitors improve outcomes in biliary tract cancer (BTC), but resistance is a challenge. This review explores emerging treatments, resistance biomarkers, and strategies to overcome them in advanced BTC.

Area of Science:

  • Oncology
  • Gastroenterology
  • Pharmacology

Background:

  • Biliary tract cancer (BTC) treatment has advanced with targeted therapies.
  • Immune checkpoint inhibitors (ICI) combined with chemotherapy show improved survival in BTC.
  • Resistance to these novel therapies is a significant clinical challenge.

Purpose of the Study:

  • To review emerging targeted therapies for BTC.
  • To discuss evolving biomarkers associated with treatment resistance.
  • To analyze strategies for overcoming resistance and ongoing clinical trials.

Main Methods:

  • Literature review of targeted therapies and ICI in BTC.
  • Analysis of pre-clinical and clinical studies on resistance mechanisms.
  • Summary of ongoing clinical trials for advanced BTC.

Main Results:

  • Targeted agents and ICI offer survival benefits but face primary and secondary resistance.
  • Combinatorial approaches are being investigated to mitigate resistance.
  • Toxicity profiles of combination therapies require careful consideration.

Conclusions:

  • Despite advances, overcoming resistance remains critical for improving long-term outcomes in BTC.
  • Further research into novel combinations and biomarkers is essential.
  • Ongoing clinical trials will define future treatment paradigms for advanced BTC.
Keywords:
Biliary tract cancerImmunotherapyResistance mechanismTargeted treatment

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