Key result
EGFR-TKIs alter cardiomyocyte mechanics, with osimertinib showing the strongest and afatinib the weakest effect.
Why the study?
Cardiac adverse events related to EGFR-TKI treatment for NSCLC occur frequently but remain poorly understood at the cellular level.
AFM-detected cardiomyocyte changes with EGFR-TKIs warrant monitoring caution in NSCLC; leaves open clinical relevance of these physical properties.
The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) has become one of the important targeted drugs for the treatment of non-small cell lung cancer (NSCLC). But the cardiac adverse events (AEs) related to the EGFR-TKI treatment occur frequently. And the cases of TKI-associated cardiac AEs remain poorly understood. In order to study the effects of EGFR-TKIs on cardiomyocytes, atomic force microscopy (AFM) was used to measure and analyze the physical properties of cardiomyocytes under the actions of three drugs (gefitinib, afatinib and osimertinib) with different concentrations. By comparing the height, adhesion, Young's modulus, the amplitude and the time of the contraction and relaxation process, it was found that the changes of the mechanical properties of cells were well correlated with the symptoms of AEs, such as cardiomyocyte hypertrophy, QT prolongation, atrial fibrillation, ejection fraction reductions, and cardiac failure. In addition, osimertinib has the most obvious effect on cardiomyocytes at a low concentration, and gefitinib has the greatest effect with the increase of concentration, while afatinib has the least effect on cardiomyocytes. This provides a new method for screening drugs and exploring the principle of action in the process of cancer treatment at the cellular level.
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Cheng et al. (2023) studied TKI-associated cardiac adverse events. EGFR-TKIs (gefitinib, afatinib, and osimertinib) was evaluated on Physical properties of cardiomyocytes (height, adhesion, Young's modulus, amplitude and time of contraction and relaxation). EGFR-TKIs altered cardiomyocyte mechanical properties, with osimertinib showing the most obvious effect at low concentrations and afatinib having the least effect.
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