Oncology drugs: Target organ findings seen in animal toxicity testing

Area of Science:

• Pharmacology
• Toxicology
• Oncology Drug Development

Background:

• Nonclinical toxicity evaluation is mandatory for oncology drugs before clinical trials.
• Oncology drugs can be inherently toxic, necessitating identification of potential target organs for patient monitoring.
• Current preclinical testing aims to predict clinical toxicities and ensure patient safety.

Purpose of the Study:

• To evaluate toxicity studies supporting clinical entry for 60 small molecule oncology drug candidates.
• To identify common target organs across various body systems in both rodent and non-rodent models.
• To assess the relationship between drug candidate target organs and tumor site interactions.

Main Methods:

• Analysis of toxicity data from preclinical studies of 60 small molecule oncology drug candidates.
• Inclusion of data from both rodent and non-rodent animal models.
• Categorization of affected body systems based on toxicity findings.

Main Results:

• The most frequently affected organs were lymphoid, gastrointestinal, bone marrow/hematologic, and liver in both rodent and non-rodent models.
• Kidney and male reproductive organs were also commonly affected, with female reproductive organs, endocrine, bone, and skin affected less frequently, primarily in rodents.
• Target organ identification was largely independent of the drug's interaction with tumor cell components (nucleus, cytoplasm, membrane receptors).
• None of the observed toxicities precluded the drug candidates from advancing to clinical trials.

Conclusions:

• Preclinical toxicity testing is crucial for identifying potential target organs and guiding patient monitoring in oncology drug development.
• The identified common target organs provide valuable insights for risk assessment.
• The findings suggest a potential need to re-evaluate the current extent of preclinical toxicity testing paradigms for oncology drugs.