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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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Modernizing Human Cancer Risk Assessment of Therapeutics

Mark R Fielden1, Lucas D Ward1, Sheroy Minocherhomji1

  • 1Amgen, One Amgen Center Drive, Thousand Oaks, CA, USA.

Trends in Pharmacological Sciences
|December 16, 2017
PubMed

Insights

Traditional rodent models for cancer risk assessment in therapeutics show poor translatability. New human-based models and biomarkers are needed to accurately evaluate therapeutic cancer risk.

Area of Science:

  • Oncology
  • Toxicology
  • Genetics

Background:

  • Rodent models for evaluating therapeutic cancer risk have limitations in translatability to human outcomes.
  • Understanding cancer mechanisms and human genetic variations is crucial for accurate risk assessment.

Purpose of the Study:

  • To review and highlight new approaches for assessing the carcinogenic risk of therapeutics.
  • To explore the development of human-based in vitro models and biomarkers for cancer risk evaluation.

Main Methods:

  • Review of current literature on carcinogenesis and therapeutic risk assessment.
  • Discussion of advancements in understanding human genome variation's role in cancer.
  • Exploration of novel human-based in vitro models and biomarker strategies.

Main Results:

  • Identified limitations in current rodent-based cancer risk assessment models.
  • Highlighted the importance of human-specific data and models.
  • Proposed a shift towards human-based in vitro systems and biomarkers.

Conclusions:

  • New human-based in vitro models and biomarkers offer improved accuracy for therapeutic cancer risk assessment.
  • Integrating knowledge of carcinogenesis mechanisms and human genetics is key.
  • This approach promises more reliable evaluation of novel therapeutics' safety.
Keywords:
carcinogenicitygenome-wide association studiesgenomic instabilityhuman biomarkersnext-generation sequencingreplication stress

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