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Histology Agnostic Drug Development: An Updated Review

Kevin Nguyen1, Karina Fama1, Guadalupe Mercado1

  • 1Touro University Nevada College of Osteopathic Medicine, 874 American Pacific Dr, Henderson, NV 89014, USA.

Cancers
|November 9, 2024
PubMed

Insights

Histology-agnostic therapies target genetic alterations, offering new precision oncology options. Continued research is crucial to overcome resistance and optimize patient selection for these transformative treatments.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Histology-agnostic therapies represent a paradigm shift in cancer treatment, targeting molecular alterations rather than tumor origin.
  • Key drugs like pembrolizumab, larotrectinib, and entrectinib are advancing precision oncology.

Purpose of the Study:

  • To provide a comprehensive review of current histology-agnostic drug development in oncology.
  • To analyze the mechanisms, outcomes, and biomarkers of leading histology-agnostic therapies.
  • To identify challenges and propose future directions in this field.

Main Methods:

  • Systematic review of current literature on histology-agnostic therapies.
  • Analysis of clinical trial data and outcomes for key targeted agents.
  • Exploration of resistance mechanisms and diagnostic considerations.

Main Results:

  • Several histology-agnostic therapies, including pembrolizumab and larotrectinib, show significant efficacy across various cancers.
  • Biomarker analysis is critical for patient selection, though challenges like intratumoral heterogeneity persist.
  • Drug resistance mechanisms, including adaptive signaling and neoantigen variability, impact treatment effectiveness.

Conclusions:

  • Histology-agnostic therapies hold transformative potential in precision oncology.
  • Overcoming drug resistance and refining patient selection through advanced biomarkers are essential for maximizing treatment benefits.
  • Further research and optimized clinical trial designs are needed to fully realize the potential of these targeted treatments.
Keywords:
V-raf murine sarcoma viral oncogene homolog B V600E (BRAFV600E)microsatellite instability-high (MSI-H)neurotrophic tyrosine kinase (NTRK)rearranged during transfection (RET)tissue agnostic drug developmenttumor mutational burden-high (TMB-H)

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