New Modalities and Carcinogenicity Assessment.

Area of Science:

• Drug development
• Toxicology
• Gene therapy

Background:

• Emerging drug modalities like adeno-associated virus (AAV) gene therapy, targeted protein degraders, oligonucleotides, and chimeric antigen receptor-T cell (CAR-T) therapies present challenges for human carcinogenicity risk assessment.
• Traditional methods such as genetic toxicology and rodent bioassays may require updates to adequately assess these novel therapeutic agents.

Purpose of the Study:

• To discuss updated strategies and contexts for human carcinogenicity risk assessment of emerging drug development modalities.
• To present a real-world case study evaluating the utility of rat mammary gland cell proliferation as a biomarker for carcinogenic potential.

Main Methods:

• Review of emerging drug development modalities and their implications for carcinogenicity risk assessment.
• Analysis of a case study investigating the carcinogenic potential of exogenous insulin.
• Interrogation of rat mammary gland cell proliferation as a predictive tool for carcinogenicity.

Main Results:

• Emerging therapies necessitate a re-evaluation of standard carcinogenicity assessment approaches.
• The case study provided insights into the applicability of specific mechanistic biomarkers.

Conclusions:

• Updated strategies are crucial for the accurate human carcinogenicity risk assessment of novel therapeutics.
• Mechanistic approaches, such as evaluating cell proliferation, may offer valuable adjuncts to traditional methods.