Individualized Systems Medicine (ISM) strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia
Menée sur 28 échantillons prélevés sur des patients atteints d'une leucémie myéloïde aiguë réfractaire, cette étude évalue la faisabilité d'une méthode permettant de tester, ex vivo, la sensibilité des cellules cancéreuses d'un patient à 187 molécules thérapeutiques
We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one-patient-at-a-time. ISM is based on i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients' cancer cells to 187 oncology drugs, ii) clinical implementation of therapies predicted to be effective and iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered five major taxonomic drug response subtypes based on DSRT profiles, some with distinct genomic features (e.g. MLL gene fusions in subgroup IV and FLT3-ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed significant clonal evolution, novel genomic changes potentially explaining resistance, while ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs.
Cancer Discovery 2013