hiPSCs in cardio-oncology: deciphering the genomics

Area of Science:

• Cardio-oncology
• Genomics
• Stem cell biology

Background:

• Genomic predisposition to cancer drug-induced cardiovascular toxicity is a long-standing hypothesis.
• Recent advances in human-induced pluripotent stem cells (hiPSCs) and genome-wide association studies (GWAS) allow experimental validation.
• Identifying specific genetic variants (SNPs) for drug toxicity is challenging due to the lack of familial comparison.

Purpose of the Study:

• To validate the hypothesis of genomic predisposition to cardiotoxicity from cancer drugs.
• To identify and validate causal genetic variants contributing to drug-induced cardiovascular toxicity.
• To leverage hiPSC technology for precision medicine in cardio-oncology.

Main Methods:

• Utilizing patient-specific hiPSCs for experimental validation.
• Employing genome-wide association studies (GWAS) and candidate gene association studies (CGAS).
• Implementing directed genomic editing (e.g., CRISPR) to verify causal variants and pathways.
• Conducting in vivo whole-organism studies for mechanistic understanding.

Main Results:

• hiPSC models combined with genomic studies can identify and validate causal variants for drug toxicity.
• Genomic editing in hiPSCs confirms the role of specific variants in cardiovascular toxicity pathways.
• This approach facilitates the identification of individuals at risk for cardiotoxicity.

Conclusions:

• hiPSC technology is crucial for identifying genomic variants that influence gene function and expression related to cardiotoxicity.
• Validated causative variants can guide clinical treatment decisions and personalize patient care in cardio-oncology.
• Findings from hiPSC studies can inform the development of safer oncology drugs and advance precision medicine.