Drug-Induced Liver Injury Associated With Emerging Cancer Therapies

Area of Science:

• Hepatology and Oncology Drug Development

Background:

• Targeted therapies and immunotherapies offer improved efficacy and safety for cancer treatment.
• While liver test abnormalities are common with kinase inhibitors and immunotherapy, severe hepatotoxicity is rare compared to chemotherapy.
• Mechanisms and risk factors for severe hepatotoxicity from novel oncology therapies remain poorly understood, complicating drug-induced liver injury (DILI) risk assessment.

Purpose of the Study:

• To describe the current knowledge on epidemiological and clinical characteristics of liver toxicity from novel oncology therapies.
• To summarize tools for assessing DILI risk during drug development, highlighting limitations for new cancer treatments.
• To introduce emerging tools for optimizing safety assessments and gaining mechanistic insights into DILI.

Main Methods:

• Review of current literature on hepatotoxicity associated with targeted therapies and immunotherapies.
• Analysis of existing tools and emerging methodologies for DILI risk assessment in preclinical and clinical drug development.
• Discussion of the unique considerations for safety assessments in oncology due to potential life-saving benefits.

Main Results:

• Severe hepatotoxicity from novel oncology agents is less common than with chemotherapy but requires careful monitoring.
• Existing DILI assessment tools have limitations when applied to novel cancer therapies.
• Emerging tools offer promise for better understanding and predicting DILI in oncology drug development.

Conclusions:

• Tailored safety assessments are essential for novel oncology therapies, considering the benefit-risk balance in cancer patients.
• A deeper understanding of DILI mechanisms, frequency, severity, and prognosis is needed.
• Streamlining drug development and regulatory processes through improved DILI assessment is critical for patient safety.