Kathryn J Crawford1, Damian G Downey1,2. 1. Northern Ireland Regional Adult Cystic Fibrosis Centre, Belfast Health and Social Care Trust. 2. Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
Abstract
PURPOSE OF REVIEW: The treatment of cystic fibrosis (CF) with CF transmembrane conductance regulator (CFTR) modulators continues to develop at a fast pace. These compounds are potentially disease modifying but are only available to certain patient subsets based on genotype. This review discusses the role of theratyping in CF and the potential to assess all patients' response to current and emerging therapies. RECENT FINDINGS: There are limitations to treatment determined by mutation, as variable clinical response to CFTR modulators has been observed within the same genotype. Patients with rare mutations not currently licensed for CFTR modulator therapy have demonstrated response to these medications. Patient-specific cellular models called organoids can be used to demonstrate response to different CFTR modulators in vitro prior to their clinical application and represent a method of theratyping. SUMMARY: Theratyping charts patients' clinical response to different treatments on an individual basis. This overcomes the limitations of genotype being used to predict response to individual therapies and includes all patients regardless of mutation. The use of organoids in high throughput screening allows numerous compounds to be tested on patient-specific tissue preclinically. This could lead to the extension of theratyping beyond CFTR modulators.
PURPOSE OF REVIEW: The treatment of cystic fibrosis (CF) with CF transmembrane conductance regulator (CFTR) modulators continues to develop at a fast pace. These compounds are potentially disease modifying but are only available to certain patient subsets based on genotype. This review discusses the role of theratyping in CF and the potential to assess all patients' response to current and emerging therapies. RECENT FINDINGS: There are limitations to treatment determined by mutation, as variable clinical response to CFTR modulators has been observed within the same genotype. Patients with rare mutations not currently licensed for CFTR modulator therapy have demonstrated response to these medications. Patient-specific cellular models called organoids can be used to demonstrate response to different CFTR modulators in vitro prior to their clinical application and represent a method of theratyping. SUMMARY: Theratyping charts patients' clinical response to different treatments on an individual basis. This overcomes the limitations of genotype being used to predict response to individual therapies and includes all patients regardless of mutation. The use of organoids in high throughput screening allows numerous compounds to be tested on patient-specific tissue preclinically. This could lead to the extension of theratyping beyond CFTR modulators.